TMC4 (transmembrane channel like 4) functions as a voltage-gated chloride channel that plays a crucial role in high-concentration salt taste sensation 1. The protein is strongly expressed in circumvallate and foliate papillae that project to the glossopharyngeal nerve, where it mediates responses to high-concentration NaCl 1. Mechanistically, TMC4 operates as a voltage-dependent chloride channel whose currents are completely inhibited by NPPB, an anion channel blocker 1. During salt taste perception, depolarization induced by high NaCl concentration triggers TMC4-mediated chloride influx into taste bud cells, helping restore the resting potential 1. While TMC4 allows permeation of organic anions including gluconate, chloride generates the strongest current amplitudes at positive potentials 1. Recent studies demonstrate that TMC4 can be activated by salty peptides, with the receptor specifically recognizing uncharged peptides through distinct binding pockets 2. Beyond taste sensation, genome-wide association studies have identified TMC4 variants associated with nonalcoholic fatty liver disease risk 3, and differential expression analysis suggests potential involvement in ankylosing spondylitis pathogenesis 4. These findings establish TMC4 as both a specialized taste receptor and a gene with broader metabolic disease associations.