Tmc1, short for Transmembrane channel-like protein isoform-1, is a prime candidate for the mechano-electrical transducer (MET) channel in hair cells of the inner ear. It is thought to have a six-transmembrane domain structure and localizes to the tips of stereocilia in the sensory hair bundle, where the MET channel is located. Mutations in Tmc1 are linked to human deafness, highlighting its crucial role in auditory function [1].

Tmc1 mutant mice have been used to study its function. For example, in Tmc1;Tmc2 double knockout mice, mechanotransduction currents are lost in hair cells, indicating the involvement of Tmc1 in auditory mechanotransduction [3]. Also, specific Tmc1 mutations in mice, like Tmc1 p.T416K and others, cause deafness and outer hair cell loss, and affect MET channel properties such as Ca2+ permeability, resting open probability, and single-channel conductance [2].

In conclusion, Tmc1 is essential for the mechanotransduction process in cochlear hair cells, which is fundamental for hearing. Studies using Tmc1 mutant mouse models have significantly advanced our understanding of how Tmc1 mutations lead to deafness, providing insights into the molecular mechanisms underlying auditory function and potential therapeutic targets for hearing loss [2,3].