TMC2

TMC2, or transmembrane channel-like 2, is a protein encoded by the TMC2 gene and a member of the transmembrane channel-like (TMC) family. It is widely studied for its proposed role in the hair cell mechanotransduction (MET) complex of the inner ear, where sensory hair cells convert mechanical stimuli from sound and head movement into neural signals.

In mammals, TMC2 is expressed in cochlear and vestibular hair cells during embryonic development and the early postnatal period. In many species its expression declines after the onset of hearing, giving way to TMC1 as a more predominant MET component in mature cochlear hair cells; however, TMC2 can persist in some vestibular cells and may contribute to residual MET currents in developing ears.

Function and mechanism: TMC2 is thought to be either a pore-forming subunit of the MET channel or a closely associated component that regulates channel properties. It likely operates together with other MET complex proteins, including TMC1, LHFPL5, PCDH15, and CDH23. Experimental evidence from knockout mice and heterologous expression studies suggests that TMC2 contributes to mechanically activated currents, and that in some contexts TMC2 can compensate partially for loss of TMC1, indicating overlapping roles.

Clinical relevance and research status: In humans, pathogenic variants in TMC2 have not been as clearly linked to hereditary deafness as TMC1. Research continues to define the exact assembly, stoichiometry, and gating mechanism of the hair cell MET channel and the specific role of TMC2 within it. Ongoing work includes in vivo studies in mice and structural analyses to resolve how TMC2 interacts with other MET components and how developmental regulation shapes hair cell function.