The results suggest that the two monomers function independentlyand underscore the critical role of lipids in shaping the pore architecture.Potential molecular mechanisms of M654V-associated pathogenicity includedisrupted local interactions between transmembrane α-helicesand residue 654, leading to reduced pore flexibility, a shifted chokepoint, and fewer lipid molecules incorporated into the pore walls.These findings provide mechanistic insights into TMC1 function andits impairment in deafness-associated variants. This evidence concerns the gene TMC1 and deafness.