SLC26A5 (prestin) is a voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility, enabling sound amplification in the cochlea 1. The protein converts transmembrane electrical potential changes into mechanical displacements through a hybrid voltage-sensing mechanism involving both intrinsic charged amino acid residues and extrinsic chloride anion binding 2. Upon depolarization, anion binding transitions the protein from an inward-open to occluded state, causing cell contraction and length changes essential for cochlear amplification 2. Salicylate inhibits electromotility by competing for the anion-binding site and preventing conformational transitions 2. Beyond hearing, prestin functions as a weak Cl⁻/HCO₃⁻ antiporter regulating OHC intracellular pH and serves as an elastic element amplifying cardiac myocyte contractility 3. Mutations in SLC26A5 cause autosomal recessive nonsyndromic hearing loss (DFNB61) 4. The p.R130S variant impairs prestin motor kinetics and causes progressive OHC degeneration and congenital hearing loss 4. Gene therapy using engineered OHC-specific enhancers successfully restored hearing in SLC26A5 knockout mice, demonstrating therapeutic potential 5.