Several members of the KIFs are implicated in the proliferative processes of neural progenitor cells. Notably, KIF20B, a constituent of the Kinesin-6 subfamily, exhibits robust expression in embryonic neural progenitors. Disruption of its functional capacity has been shown to diminish the proliferation of both neural progenitor cells (NPCs) and neuronal lineages within the cerebral cortex. Consequently, this reduction culminates in a cortical layer that is proportionally thinner compared to the norm, highlighting the indispensable role of KIF20B in the context of neural development (Janisch et al., 2013). KIF20A, another member of the Kinesin-6 family, has been identified as playing a crucial role in maintaining the proliferative state of NPCs during the development of the cerebral cortex. Knockout studies of KIF20A have demonstrated that NPCs in the cerebral cortex transition from a proliferative and dividing state to a differentiated state, which is accompanied by the apoptosis of progenitor cells and neurons. This shift ultimately leads to cortical thinning and ventriculus cerebri enlargement. Notably, partial loss of KIF20A function results in the exit of neurons from the cell cycle and the premature differentiation of neurons; however, it does not induce significant defects in cell division or apoptosis (Geng et al., 2018; Qiu et al., 2020). Other members of KIFs, including KIF15 (Feng et al., 2016) and KIF3A (Tong et al., 2014; Feng et al., 2016; Cullen et al., 2021), have been implicated in the proliferation and differentiation of neural progenitor cells. Furthermore, according to the study published by Naher et al. (2025), KIF23 was a key molecule regulating neural stem cell development, and its loss of function can directly lead to the pathological mechanism of microcephaly. The study of Naher et al. (2025) not only reveals the key role of KIF23 in maintaining the neural stem cell pool during embryonic brain development but also provides a molecular basis for the genetic diagnosis and treatment of microcephaly through the elucidation of the pathogenic mutation mechanism. This suggests that future studies need to further explore the function of KIF23 in primate models and the window of clinical intervention to promote the transformation from mechanism discovery to treatment (Naher et al., 2025). These findings underscore the significant role of KIFs in cerebral development, particularly in the context of the proliferation and differentiation of neural progenitor cells within the cerebral cortex. The functional involvement of these kinesin family members during neurogenesis highlights their potential as key regulatory factors in the construction and refinement of the neural architecture.

Neuronal migration denotes the orchestrated relocation of immature neurons through time and space, ensuring their accurate arrival at their predetermined functional destinations within the neural architecture. This process is meticulously regulated and is fundamental to the proper formation and functionality of neural circuits. KIFs are also instrumental in the process of neuronal migration, highlighting their essential roles in the orchestration of neuronal positioning and the subsequent refinement of neural circuits.

KIF2A is an ATP-dependent microtubule depolymerizing factor that plays a critical role in regulating microtubule dynamics. Specifically, the targeted ablation of KIF2A in inhibitory forebrain neurons leads to aberrations in the tangential migration of interneurons within the cortex, subsequently affecting their proper cortical localization (Ruiz-Reig et al., 2022a). Additionally, it has been observed that the downregulation of KIF20B levels impedes the transition of multipolar cells from a multipolar to a bipolar state in the ventricular zone, thereby inhibiting neuronal migration. These findings underscore the significance of KIF20B in the dynamic processes underlying neuronal polarization and migration (Sapir et al., 2013). Furthermore, additional research into the developing rodent brain has revealed that KIF15 is markedly enriched in migrating neurons relative to their non-migrating counterparts (Buster et al., 2003). Subsequent studies have demonstrated that KIF15 directly interacts with myosin-IIB through its tail domain, thereby modulating the proliferation of neuronal precursor cells and the migratory behavior of immature neurons. This protein is not only implicated in neuronal migration but also plays a role in the migration of astrocytes (Feng et al., 2016). KIFC1, a member of the Kinesin14 family, is capable of propelling microtubule sliding, which facilitates the directional rotation of the nucleus during neuronal migration, thereby ensuring that these cells remain on their intended trajectory. The absence of KIFC1 leads to deviations in the migratory path of neurons, highlighting the essential role of KIFC1 in maintaining the fidelity of neuronal migration trajectories (Muralidharan et al., 2022). Collectively, these findings underscore the significant impact of KIFs on the migratory processes of neurons.

Kinesin superfamily proteins are principal molecular motors protein that play a crucial role in intracellular transport. Specific members of the KIFs are tasked with the conveyance of assorted “cargos” along microtubules to the axonal and dendritic compartments of neurons. This vesicular transport is integral to the modulation of neuronal status and cerebral function, encompassing the regulation of “cargo” trafficking, as well as the growth and functional sustenance of axons and dendrites.

KIF1A is predominantly engaged in the axonal transport of synaptic vesicle precursors (SVPs) along microtubules, exerting a pivotal role in the viability and functional preservation of mature neurons (Okada et al., 1995). Yonekawa et al. (1998) found that, in neurons with KIF1A mutations, the transport of SVPs is markedly diminished, culminating in an inability to adequately receive afferent stimuli, inclusive of neuronal contact and neurotransmission. This deficiency ultimately precipitates neuronal demise (Yonekawa et al., 1998). However, another study found that the KIF1A mutation associated with hereditary spastic paraplegia would lead to excessive activation of KIF1A movement, thereby causing abnormal accumulation of SVPs at axon tips, and increases the anterograde axonal transport of SVPs. This change can disrupt the homeostasis of human motor neurons and is one of the causes of motor neuron diseases (Chiba et al., 2019). Niwa et al. (2008) first identified KIF1Bβ as working together with KIF1A to mediate the axonal antegrade transport of SVPs. Subsequently, Xu et al. (2018) further revealed that KIF1Bβ undertakes a variety of cargo transport tasks in neurons, beyond the category of synaptic vesicles, including mitochondrial transport and the transport of neurotrophin-receptor TrkA. In summary, the synergistic action of KIF1A and KIF1Bβ ensures efficient synaptic vesicle trafficking, and the independent function of KIF1Bβ in mitochondrial and TrkA receptor trafficking further expand the regulatory dimension of kinesins in neuronal survival and disease. Within the same KIFs, the ablation of KIF1B elicits aberrations in synaptic transport and is associated with impaired axonal elongation (Xu et al., 2018). The primary role of KIF17 within the Kinesin2 family is to facilitate the intracellular trafficking of the N-methyl-D-aspartate receptor NR2B subunit, the metabotropic glutamate receptor 5, and the potassium channel Kv4.2 from the cell soma to the dendrites. This transport process is pivotal for cognitive functions such as learning and memory. Subsequent research has corroborated that the absence or dysfunction of KIF17 leads to deficits in the learning capabilities and spatial memory retention of rodents (Wong et al., 2002; Wong-Riley and Besharse, 2012; Yin et al., 2012).

Dysfunctional KIFs members can significantly impact on neuronal morphology. Neurons deficient in KIF2A exhibit aberrant electrophysiological properties and atypical growth patterns of dendritic collaterals (Homma et al., 2003, 2018; Akkaya et al., 2021; Ruiz-Reig et al., 2022b). The downregulation of KIF3B in neurons results in an excessive proliferation of dendritic spines and branches, suggesting that KIF3B plays an inhibitory and regulatory role in the structural plasticity of neurons (Joseph et al., 2020). Furthermore, KIF3B knockdown has been associated with impaired contextual fear memory in mice (Alsabban et al., 2020; Joseph et al., 2021; Yoshihara et al., 2021). In contrast, the knockdown of KIF3A, KIF5 (comprising KIF5A, KIF5B, and KIF5C), and KIF11 has been shown to have the opposite effect to KIF3B, leading to a reduction in dendritic branching and spine density (Liu et al., 2010; Zhao et al., 2020; Lucero et al., 2022). KIF5C is a key regulator of excitatory synaptic transmission, structural plasticity, and local translation. Experiments have shown that the loss of KIF5C function in dorsal CA1 neurons of horses is related to the attenuation of spatial and situational fear memory, because this process reduces dendritic branch formation and spinal density, which affects the learning and memory ability of the body (Swarnkar et al., 2021). Recent studies have revealed that the deletion of KIF2C can significantly alter the density of dendritic spines within the hippocampus of mice, resulting in impaired excitatory synaptic transmission and alterations in cognitive behavior (Zheng et al., 2022). Our research group has conducted corroborative studies on the role of KIF2C, which have substantiated these findings. Building upon this foundation, we have discovered that the absence of KIF2C also leads to aberrant dendritic branching and spine formation in the cerebral cortex of mice, consequently impacting their cognitive function. Furthermore, we intend to delve deeper into the mechanistic underpinnings of these phenomena through a comprehensive investigation. Collectively, these findings underscore the indispensable role of KIFs in the morphological and functional regulation of neuronal integrity.

Abnormal expression of KIFs can lead to cell mitosis disorder and cell genomic instability. Genome instability, in particular, is a key factor in transformation of cells into cancer and tumor. Many clinical data have confirmed the involvement of KIFs in the occurrence and development of various malignant tumors (Chen et al., 2017; Lucanus and Yip, 2018; Ghnim et al., 2024; Yang et al., 2021). Schlisio et al. (2008) first established that KIF1Bβ is a key tumor suppressor gene in neuroblastoma, and the expression of KIF1B is significantly downregulated or even absent in a variety of neural crest derived tumors such as neuroblastoma, pheochromocytoma, and glioma. KIFs members have been found to play significant role in the disease progression of brain tumors.

Glioma is one of the most common primary malignant tumors in adults, mainly occurring in brain and glial tissues, and has a very high mortality due to its localization and powerful invasive ability (Ostrom et al., 2014). The median survival of glioma patients is only 14–16 months (Louis et al., 2016). It is classified into grades 1–4 according to the degree of malignancy. KIFs members (KIF1A, KIF1B, KIF2A, KIF3C, KIF4A, KIF9, KIF13A, KIF13B, KIF14, KIF15, KIF18A, KIF20A, KIF22, KIF23, KIF15, KIF18A, KIF20A, KIF22, KIF23, KIF26A) are highly expressed in glioma tissues (Wang et al., 2013; Chen et al., 2016; Sun et al., 2016; Zhang et al., 2016, 2022; Saito et al., 2017; Cho et al., 2019; Gao et al., 2020b; Iegiani et al., 2021; Ren et al., 2022; Tao et al., 2022; Pan et al., 2023), and are more expressed in glioma tissues with high malignant degree (Zhang et al., 2016). Moreover, the expression level of KIF is negatively correlated with the prognosis and survival of patients (Chen et al., 2016). Subsequent studies have found that downregulate the expression levels of these KIF members can inhibit the proliferation, invasion and migration of glioma cell lines (Saito et al., 2017; Gao et al., 2020b; Zhang et al., 2022). For example, KIF3C may promote the proliferation, migration and invasion of glioma cells by activating the PI3K/AKT/mTOR pathway in vitro, inhibit the apoptosis of cancer cells, and prolong survival time. Inhibition of KIF4A can inhibit the progression of glioma, and addition of a small molecule inhibitor of KIF4A induced apoptosis in glioma cells, showing anti-glioma effects. These results suggest that these KIFs members may become new predictors and therapeutic targets for gliomas.

Meningiomas (MGMs) are also one of the most common types of central nervous system tumor, accounting for one-third of all brain tumor (Mawrin and Perry, 2010). MGMs are histologically classified according to the WHO grading scheme: nearly 80% of MGMs are benign, corresponding to WHO°I, 10%–15% are atypical (WHO°II), and only 2%–5% are anagenic MGMs WHO°III (Louis et al., 2007). Among them, the survival rate of benign MGM patients is 92%, the survival rate of atypical MGM drops to 78%, and the survival rate of WHO° Grade III MGM patients is only 47% (Durand et al., 2009; Vranic et al., 2010; Gousias et al., 2016). Durand et al. (2009) analyzed a microarray dataset of benign, atypical, and anaplastic MGMs and obtained differential expression of five driver proteins (KIFC1, KIF4A, KIF11, KIF14, and KIF20A) that are significantly upregulated in WHO°I to°III MGMs. Later studies find that knocking down KIF11 in anaplastic MGM cell line NCH93 inhibited 71% of tumor cell proliferation (Jungwirth et al., 2019). Subsequent studies have shown that KIF11 inhibitors filanesib and ispinesib can induce G2/M stagnation in all MGM cell lines and significantly inhibit the growth rate of MGM in mice in vivo up to 83% (Jungwirth et al., 2021), indicating that inhibiting the function of KIF11 may be one of the ways to treat MGMs.

Stroke is an acute cerebrovascular disease, which is a group of diseases caused by brain tissue damage due to the sudden rupture of blood vessels in the brain or the blockage of blood vessels that prevents blood from flowing to the brain, including ischemic and hemorrhagic stroke. The onset age of stroke is more over 40 years old, and has long been a major cause of death in China (Wang et al., 2024). O’Connell et al. (2017) obtain publicly available whole blood microarray data generated 3, 5, and 24 h after symptom onset in 23 ischemic stroke patients, and 23 cardiovascular disease controls using the National Center for Biotechnology Informatics Gene Expression Synthesis. There are 10 candidate genes with expression levels that distinguish stroke patients from controls, including KIF1B (O’Connell et al., 2017). The other study has found that KIF2 is abnormally expressed in the brain tissue of middle cerebral artery occlusion rat model in a time-dependent manner, and inhibition of KIF2 significantly increases the level of malondialdehyde in the brain tissue of middle cerebral artery occlusion model and decreases the activities of superoxide dismutase and glutathione peroxidase. Increase the severity of the disease. It is also found that KIF2-mediated nuclear factor-kappa B (NF-κB) pathway is involved in neuroprotection after cerebral ischemia/reperfusion injury, and the addition of NF-κB pathway inhibitors can reduce the apoptosis of KIF2-silenced hypoxic cells (Wang et al., 2020). This may provide a new diagnostic indicator and therapeutic target for strokes.

Schizophrenia (SCZ) is a major psychiatric disorder affecting many aspects of behavior and cognition, with a global lifetime prevalence of 1% (Andreasen, 1995). According to the neurodevelopmental hypothesis of the pathogenesis of SCZ, neuronal dysplasia occurring at various stages of neurodevelopment will predispose individuals to SCZ (Birnbaum and Weinberger, 2017). Studies have shown that cerebral anatomical will change in patients with SCZ, such as reduced cortical volume, ventricular enlargement, and reduced cortical gray matter (Kochunov and Hong, 2014). In addition, clinical autopsy finds that the expression level of KIF3 is down-regulated in the prefrontal cortex of SCZ patients after death, and Kif3b^± mice show obvious schizophrenia traits such as social disturbance and postsynaptic defects in follow-up studies (Alsabban et al., 2020; Yoshihara et al., 2021). Other researchers conduct differential gene screening on a large number of SCZ patients from Iran and Shandong, China, and find that the KIF26B mutant may be a novel genetic biomarker of SCZ susceptibility in these two places (Zhang and Chen, 2020; Sargazi et al., 2021). Analysis of some SCZ family samples also find that KIF2 gene in the 5q12.1 region (Li et al., 2006) and KIF13A (Jamain et al., 2001) in the 6p23 region may also be candidates for genetic susceptibility genes for SCZ.

Kinesin superfamily proteins may also be related to suicidal tendencies. Niculescu et al. (2015) analyzed the blood samples of patients with suicidal tendencies, such as bipolar disorder, major depression, schizoaffective disorder and SCZ, and find that KIF2C is significantly reduced in the blood samples of patients with strong suicidal tendencies. In addition, Cabrera-Mendoza et al. (2020) evaluate the differences in DNA methylation between individuals with high and low suicidal tendencies, then find that KIF7 is differentially expressed between the two groups. These two studies indicate that the differential expression of KIFs has certain reference significance for the prediction and diagnosis of clinical suicidal tendency. Which can increase the observation and protection of suspected patients, reduce the suicide rate, and conduct in-depth research on whether it is a pathogenic factor and develop symptomatic treatment.