1.A.84.1.1
The human calcium homeostasis modulator protein 1, CALHM1 or FAM16C of 346 aas and 5 TMSs (Dreses-Werringloer et al. 2008).  The P86L polymorphism increases Abeta levels and may influence Alzheimer's disease risk by interfering with CALHM1-mediated Ca²⁺ permeability (Dreses-Werringloer et al. 2008). The characteristics of this channel have been  studied (Ma et al. 2012) and reviewed (Ma et al. 2015). Post-translational palmitoylation controls the voltage-gating and lipid raft association (Taruno et al. 2017). CALHM1 plays a role, complementary to PANX1 (TC#1.A.25.2.1), in ATP release and downstream ciliary beat frequency modulation following a mechanical stimulus in airway epithelial cells (Workman et al. 2017). CALHM1 is required for sensory perception of sweet, bitter and umami tastes. It is present in type II taste bud cells, where it plays a central role in taste perception by inducing ATP release from the cell with ATP acting as a neurotransmitter to activate afferent neural gustatory pathways. It acts both as a voltage-gated and calcium-activated ion channel mediating neuronal excitability in response to changes in extracellular Ca²⁺ concentration (Bhat et al. 2021). It has poor ion selectivity and forms a wide pore (around 14 Å) that mediates permeation of Ca²⁺, Na⁺ and K⁺, as well as monovalent anions. It acts as an activator of the ERK1 and ERK2 cascade and triggers endoplasmic reticulum stress by reducing the calcium content of the ER (Gallego-Sandín et al. 2011). It may indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptide levels in a Ca²⁺ dependent manner (Dreses-Werringloer et al. 2008). The ATP comes from unusually large mitochondria that are adjacent to clusters of CALHM1 channels in the plasma membrane (Romanov et al. 2018). Thus, neurotransmission does not rely on vesicle formation. Intramolecular disulfide bonds for biogenesis of CALHM1 ion channels are dispensable for voltage-dependent activation (Kwon et al. 2021).  Intracellular Ca²⁺ oscillation frequency and amplitude modulation mediate epithelial apical and basolateral membranes crosstalk (Hassan et al. 2024).