OTOP1 (otopetrin 1) is a proton-selective ion channel with biphasic activation properties that functions primarily in taste sensation and inner ear physiology. As the sour taste receptor, OTOP1 mediates inward proton currents in response to extracellular acidification in Type III taste receptor cells 1. Beyond acid sensing, OTOP1 functions as a sensor for ammonium chloride, wherein extracellular NH4Cl alkalinizes the cytosol, generating a driving force for proton influx through the channel 2. The channel exhibits distinct gating mechanisms: acid activation involves residues H229 and R292, while alkali activation (mediating proton efflux) requires K221 and R554, suggesting independent activation pathways 34. OTOP1 also exhibits alkali-sensitivity, potentially participating in alkaline taste sensation 4. Evolutionarily, avian OTOP1 variants show acid-induced inhibition enabling sour tolerance in birds consuming acidic fruits 5. Functionally, N-glycosylation at N238 and N251 residues in the extracellular S5-6 loop is essential for plasma membrane targeting and maximum current density 6. The channel responds to allosteric modulators including carvacrol and small molecule enhancers, with critical gating elements located in transmembrane segments and extracellular loops 78. OTOP1's role extends beyond taste to inner ear otolith formation and potentially metabolic homeostasis regulation.