Pore-forming subunit of a voltage-gated ion channel, also permeable to larger molecules including ATP, required for sensory perception of sweet, bitter and umami tastes (PubMed:23467090). Specifically present in type II taste bud cells, where it plays a central role in sweet, bitter and umami taste perception by inducing ATP release from the cell, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (PubMed:23467090). Together with CALHM3, forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells (TBCs) (PubMed:29681531). Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration (PubMed:22711817). Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of Ca(2+), Na(+) and K(+), as well as permeation of monovalent anions (PubMed:22711817). Acts as an activator of the ERK1 and ERK2 cascade (By similarity). Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum (By similarity). May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+) dependent manner (By similarity). Inhibited by Gd(3+), Ruthenium Red, and Zn(2+) and partially inhibited by 2-aminoethoxydiphenyl borate. Homohexamer (By similarity). Associates with CALHM3 as a pore-forming subunit in an hetero-hexameric channel complex (PubMed:29681531). Localizes to the basolateral membrane of epithelial cells including taste cells (PubMed:30804437). Colocalizes with HSPA5 at the endoplasmic reticulum (By similarity). Specifically expressed in type II taste bud cells. Not expressed in brain. Impaired perceptions of sweet, bitter and umami compounds. Mice are viable and fertile, with no visible morphological abnormalities in their taste buds or any altered expression of taste-related marker genes. They do however display a loss of both preference for sweet and umami compounds and for avoidance of bitter compounds. Perceptions of sour and salty tastes are unaffected. Reduced voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Elderly males and females do not show defects in spatial learning and memory retrieving. Belongs to the CALHM family.