CALHM3 is a pore-forming subunit of voltage-gated ion channels essential for taste perception. It heterodimerizes with CALHM1 to form a large-conductance, fast-activating channel in the basolateral membrane of type II taste bud cells 1. This CALHM1/CALHM3 hexameric complex mediates non-vesicular ATP release in response to membrane depolarization triggered by sweet, bitter, and umami tastant binding to GPCRs 12. Released ATP acts as a neurotransmitter, activating P2X2 and P2X3 purinergic receptors on gustatory afferent neurons to transmit taste signals 2. The channel exhibits poor ion selectivity, forming a wide pore (~14 Ångströms) permeable to small ions (Ca²⁺, Na⁺, K⁺, Cl⁻) and larger molecules like ATP⁴⁻ 3. CALHM3 function is regulated by posttranslational modifications: N-glycosylation controls biosynthesis and gating kinetics, while S-palmitoylation by DHHC3 and DHHC15 is critical for channel activity 4. Genetic deletion of Calhm3 abolishes taste-evoked ATP release and GPCR-mediated taste perception 1. The channel demonstrates intrinsic basolateral sorting through canonical and non-canonical signals, enabling proper localization at synaptic contact sites with nerve fibers 5.