CALHM1 is a voltage-gated, calcium-activated ion channel that functions as a pore-forming subunit with broad physiological roles. In taste sensation, CALHM1 forms an action potential-dependent ATP-release channel with CALHM3 in type II taste bud cells, mediating neurotransmitter release for sweet, bitter, and umami taste perception 1. The channel exhibits poor ion selectivity with a wide ~14 Ångström pore permitting Ca²⁺, Na⁺, K⁺, Cl⁻, and ATP permeation 2. CALHM1 gating is allosterically regulated by membrane voltage and extracellular Ca²⁺ concentration, with the amino-terminal helix and first transmembrane domain contributing to voltage-dependent gating 3. In neurons, CALHM1 mediates Ca²⁺ influx and downstream ERK1/2 cascade activation, while also triggering endoplasmic reticulum stress through Ca²⁺ depletion 4. Structurally, CALHM1 exists as a hexameric assembly with conserved lipid-binding pockets regulating channel activity 2. Disease relevance includes potential Alzheimer's disease involvement through amyloid-β metabolism regulation; the rare R154H variant impairs Ca²⁺ uptake and Aβ control, while the common G330D variant shows no functional consequences 5. Meta-analysis suggests the rs2986017 polymorphism associates with increased AD risk in Caucasian populations 6.