TM is a highly hydrated extracellular matrix located above the mechanosensory hair cell bundles in the cochlea. The TM’s three main constituents are water (97%), glycosaminoglycans and collagen fibers (collagen II, IX, and XI), and non-collagenous proteins, such as α-tectorin, β-tectorin, CEACAM16, otogelin, and otogelin-like. The prominent feature of the TM is the thick collagen bundles running radially. These bundles are composed of 20 nm diameter collagen filaments imbedded in a tectorin-based striated-sheet matrix (2). The TM is closely associated with the stereocilium of the outer hair cells.

The mechanical connection between the TM and outer hair cells (OHCs) plays a crucial role in cochlear amplification. By stimulating the OHCs through contact with their stereociliary bundles, the TM facilitates synchronized movement of the OHC stereocilia, allowing efficient mechanical energy transfer. The horizontal top connectors, formed by otogelin, otogelin-like, and stereocilin proteins, are essential for maintaining the cohesion of OHC stereocilia and stabilizing the mechanical coupling between the TM and OHCs (3). These proteins interact together to maintain the mechanical integrity of OHC stereocilia, underscoring the importance of this coupling in cochlear amplification and mechanotransduction (3, 4).

The relationship between the tectorial membrane (TM) and inner hair cells (IHCs) has traditionally been considered indirect, with the TM modulating IHC responses via endolymphatic fluid motion or through its mechanical interaction with outer hair cells (OHCs) (5). However, recent high-resolution imaging studies have fundamentally challenged this classical view. Using laser confocal reflectance and fluorescence microscopy in ex vivo guinea pig cochleae, Hakizimana and Fridberger provided compelling anatomical evidence that IHC stereocilia, like those of OHCs, are physically embedded within the TM (6). Overlay analyses of reflected and labeled images revealed consistent continuity between the TM and stereociliary bundles in both IHC and OHC regions across multiple preparations (Figure 1).

This discovery redefines the mechanical interface of IHCs, indicating that their activation may not depend solely on hydrodynamic shearing forces but also on direct radial displacements transmitted through the TM. Such direct coupling could facilitate enhanced sensitivity, phase-locked stimulation, and improved frequency selectivity, particularly in the apical cochlea. Furthermore, Ca²⁺ ratiometric imaging revealed that the TM functions as a localized calcium reservoir. Stereocilia of both IHCs and OHCs were shown to reside within microdomains of elevated Ca²⁺ concentration, despite the typically low Ca²⁺ levels of surrounding endolymph. This TM-mediated Ca²⁺ enrichment may resolve the long-standing paradox of high MET channel open probabilities under low Ca²⁺ conditions and implies that the TM supports both mechanical and ionic prerequisites for efficient mechanotransduction.

Importantly, during acoustic stimulation, IHC and OHC stereocilia exhibited synchronized phase-locked motion within the TM, despite distinct local kinematic patterns. This further supports the hypothesis that the TM plays a direct and dynamic role in transducing mechanical stimuli to IHCs. Moreover, the TM itself propagates traveling waves (6–8), suggesting that its longitudinal motion may contribute to fine-tuned spatial activation of hair cells. Collectively, these findings warrant a revision of canonical models of cochlear micromechanics, positioning the TM as a critical structural and biochemical mediator in both OHC and IHC function (Figure 1 and Table 1).

TM plays a pivotal role in cochlear micromechanics, which is essential for sound amplification and the efficient transmission of auditory signals (9). Radial motion within the organ of Corti is tuned to the frequency of cochlear amplification rather than the frequency of the underlying basilar membrane. Radial tuning of the reticular lamina (RL) and TM has been observed even in non-functional cochleae, such as in dead cochleae and Tecta mutants, suggesting that this tuning arises from passive mechanical properties. The radial tuning of the RL and TM contributes to the selective stimulation of OHCs, playing a role in cochlear frequency selectivity (10). The role of TM in enhancing the mechanical deflection of hair bundles is limited (11).

Abnormalities in the structure and function of the TM can contribute to hearing loss, particularly through the degeneration of TM or loss of horizontal top connectors. While changes in the TM affect its elasticity and stiffness, impairing cochlear amplification (4), it should be noted that hearing loss is not directly attributable to TM dysfunction. Current diagnostic tools, such as otoacoustic emissions (OAEs), provide indirect insights into TM function, but direct clinical assessment methods for TM integrity are lacking (12). Further research is needed to understand how TM dysfunction contributes to hearing loss and to develop better diagnostic techniques.

Several studies have reported idiopathic sudden hearing loss cases exhibit abnormal TM through temporal bone dissect (1, 13–15). Fred H Linthicum Jr. et al. suggested that the analysis of temporal bones from patients with sudden sensorineural hearing loss does not support a vascular insufficiency, but rather points to a viral etiology (14). Y Nomura et al. demonstrated that direct inoculation of herpes simplex virus (HSV) into the guinea pig scala tympani induced morphological changes in the TM, including atrophy, roll-up, and dot formation, confirmed by immunofluorescent and electron microscopic evidence of HSV infection (16). Therefore, we consider whether the TM has a virus susceptibility, and the virus destroys the rigid structure of the TM, resulting in the TM losing support, curling and other morphological abnormalities. Viral infection results in malformation of the operculum, contributing to sudden hearing loss. However, the specific pathogenesis requires further investigation.

Hereditary mutations in genes encoding the TM proteins are significant contributors to TM abnormalities and associated hearing loss. These mutations impair the integrity, leading to sensorineural hearing loss, with phenotypic differences depending on the affected gene and mutation site.

Ototoxic drugs, such as aminoglycoside antibiotics (e.g., gentamicin, kanamycin), chemotherapeutic agents (e.g., carboplatin), and loop diuretics (e.g., furosemide), exert significant toxic effects on the auditory system, particularly on the structure and function of the TM in the inner ear. These drugs disrupt the transmission and amplification of auditory signals through direct or indirect effects on the TM.

As aging progresses, significant structural changes occur in the inner ear, closely associated with the development of age-related hearing loss (ARHL) or presbycusis. Studies have shown that in both aged Fischer 344 (F344) rats and human cochleae, the TM undergoes substantial degeneration. These changes include a decline in the density of the core matrix, the loss of non-collagenous glycoproteins such as TECTA, TECTB, and CEACAM16, and the separation of the TM from the spiral ligament. These alterations weaken the TM’s mechanical properties, such as mass and stiffness, thereby impairing its ability to amplify sound-induced motion and perform frequency selectivity. In F344 rats, the TM exhibits pronounced deformation and detachment from the organ of Corti. Similarly, in human samples, the characteristic TM degeneration highlights its critical role in the aging process (57). TM degeneration may precedes hair cell loss and elevated hearing thresholds, suggesting its potential involvement in the early stages of ARHL. Aging IHCs display phenomena such as stereocilia fusion, elongation, and internalization, which may further disrupt the mechanical transduction of sound signals. Together, these changes in the TM and IHC stereocilia exacerbate the decline in auditory function (58). These findings underscore the critical role of the TM in the progression of ARHL. However, the exact contributions of IHC stereocilia changes and their interactions with TM degeneration require further study. The importance of targeting these structures for potential therapeutic strategies to delay or reverse age-related hearing decline is clear, but additional research is necessary to fully understand these complex mechanisms and their therapeutic implications.

Thyroid hormone (TH) is an indispensable regulator in cochlear development, and its deficiency leads to significant structural abnormalities in the TM and profound auditory dysfunction. Studies have demonstrated that TH regulates the normal development of the TM by modulating the transformation of Kolliker’s organ (KO). Under normal conditions, TH induces the transition of KO cells from tall columnar cells to supporting cells, facilitates the formation of the tunnel of Corti and Nuel’s spaces, and terminates the secretory activity of KO. However, in hypothyroidism, the development of KO is arrested, and its persistent secretory activity results in a markedly enlarged, morphologically distorted TM with disorganized distributions of glycoproteins and carbohydrates. These abnormalities may impair the TM’s mechanical properties, weakening its ability to amplify and transmit auditory signals (59).

TH deficiency also disrupts the composition of TM components, including an increase in β-tectorin levels and abnormalities in the striated-sheet matrix structure, further reducing the TM’s mechanical functionality. Moreover, chronic damage to OHCs occurs, characterized by a permanent reduction in the expression of KCNQ4 potassium channels and delayed maturation of Prestin protein. In addition, reduced KCNJ10 channel expression in the stria vascularis of the spiral ganglion leads to a significant decrease in endocochlear potential (EP), further compromising hair cell function. These changes culminate in irreversible auditory deficits (60).

Mutations in the SLC26A4 gene, such as those associated with Pendred syndrome and DFNB4, profoundly impact TM structure and function through both TH-dependent and TH-independent mechanisms. In Slc26a4^loop/loop mice, although serum T3 and T4 levels remain normal, thyroid follicles exhibit marked atrophy, the TM becomes significantly thickened, β-tectorin expression is reduced, and cochlear bone mineralization is impaired (61). These defects are also associated with the loss of BK potassium channels in inner hair cells. Such abnormalities may result from localized TH deficiency due to inner ear fluid acidification, which impairs the activity of pH-sensitive enzymes such as type II deiodinase (D2) and reduces the conversion of T4 to T3, thereby exacerbating hearing loss.

Congenital hypothyroidism further highlights the regulatory role of TH in TM development. The TM in hypothyroid cochleae displays an abnormally enlarged and distorted morphology, with significantly disorganized distributions of glycoproteins and carbohydrates. Radiolabeled studies have revealed that the TM in hypothyroid rats exhibits a markedly increased uptake of N-acetyl-D-glucosamine, indicating dysregulated glycoprotein synthesis and secretion. These findings underscore the critical role of TH in the development of the TM, as well as in the synthesis and secretion of glycoproteins. TH deficiency may be closely associated with age-related hearing loss (presbycusis) and other auditory dysfunctions (62).

Early diagnosis of hearing loss caused by TM abnormalities is crucial for timely prevention and treatment. For patients with a family history of mid-or high-frequency hearing loss, screening for genes associated with TM function may be considered. Detection of spontaneous otoacoustic emissions (SOAE) or stimulus-frequency otoacoustic emissions (SFOAE) can help identify functional changes in outer hair cells caused by TM abnormalities at an early stage. Structural or functional abnormalities in the TM may lead to either an enhancement or a loss of OAE signals, making these diagnostic methods significantly important for early detection of potential issues. In addition, optical coherence tomography (OCT) technology provides high-resolution cochlear imaging, which aids clinicians in detecting subtle changes in the TM and other crucial cochlear structures. While this technology is primarily used in research, it holds potential as an effective tool for early diagnosis of TM abnormalities. Notably, OCT has been utilized in some hospitals for the assessment of otitis media, and its application may expand to hearing diagnostics in the future.

Electrocochleography (ECochG) is a clinical diagnostic tool commonly used to assess cochlear function, particularly the mechanical and electrical responses of the OHCs and IHCs. ECochG includes four distinct signal components: the cochlear microphonic (CM), which represents the response from outer hair cells; the auditory nerve neurophonic (ANN), reflecting the early neural response and activity from inner hair cells; the compound action potential (CAP), which is the early response from the auditory nerve; and the summating potential (SP), primarily associated with the response of inner hair cells (63–67). ECochG, while not directly assessing Tectorial Membrane (TM) integrity, can serve as an indirect method for evaluating TM function by reflecting the mechanical coupling between the TM and hair cells. Changes in TM function, such as altered OHC stereocilia motion or disrupted IHC activation, can affect the cochlear response, which is captured in the ECochG signals. Specifically, Cochlear Microphonic (CM) and Compound Action Potential (CAP) reflect the OHC response, while the Summating Potential (SP) primarily reflects IHC activity. Alterations in TM function, including disrupted mechanotransduction or calcium regulation, can lead to changes in these signals. ECochG is therefore a useful tool for indirectly assessing TM-related dysfunction by detecting deviations in these cochlear potentials, which can provide insights into the TM’s impact on cochlear amplification and mechanotransduction.

Currently, the primary treatment options for hearing loss caused by TM damage are still focused on assistive hearing devices, such as hearing aids and cochlear implants. In addition to these traditional methods, gene therapy has emerged as a new area of research, particularly the development of treatments targeting deafness-related genes associated with the TM. Currently, gene therapies mainly include gene editing techniques and gene replacement therapy. At the same time, some researchers are exploring the potential of small molecule drugs for treatment. For patients with TM damage caused by immune responses or inflammation, anti-inflammatory drugs may be used to reduce inflammation and prevent further degeneration. Additionally, stem cell therapy has shown potential application value in cochlear injury repair.

Future research should focus on optimizing the diagnosis and treatment of hearing loss associated with the TM. In the field of gene therapy, studies on genes such as TECTA, TECTB, and CEACAM16 could advance the development of CRISPR-Cas9, RNA interference (RNAi), and gene replacement therapies. Pharmacological interventions may explore small molecules to stabilize the TM structure or employ anti-inflammatory and immune modulation to prevent inflammatory damage. Furthermore, stem cell therapy and tissue engineering could provide new approaches for TM regeneration. Advanced imaging technologies, such as optical coherence tomography (OCT), combined with artificial intelligence, can enhance early diagnostic accuracy, while ion homeostasis regulation may help restore the mechanical properties and auditory function of the TM. Ultimately, precision medicine, integrating genomics and machine learning, will drive the development of personalized treatment plans, making the treatment of TM-related hearing loss more efficient and precise.