Calcium homeostasis modulator protein 1 (CALHM1)

Calcium homeostasis modulator protein 1 (CALHM1) is a multipass transmembrane protein that functions as a large-pore, non-selective ion channel and a voltage-gated ATP-release channel. It is predominantly expressed in the hippocampus and in type II taste bud cells, where it plays a critical role in the perception of sweet, bitter, and umami tastes by mediating the non-synaptic release of ATP. In the central nervous system, CALHM1 regulates neuronal excitability and intracellular calcium signaling in response to changes in membrane voltage and extracellular calcium concentrations. The protein has gained significant attention due to its involvement in Alzheimer's disease; the P86L polymorphism in the CALHM1 gene is associated with an earlier age of onset and altered amyloid-beta metabolism. Research indicates that CALHM1 promotes the clearance of amyloid-beta by facilitating the secretion of insulin-degrading enzyme (IDE). While no specific drugs are currently approved for this target, small molecules like ruthenium red and CGP37157 are used as pharmacological tools to study its function, and it remains a potential therapeutic target for neurodegenerative disorders and taste-related conditions.

Other names

FAM26CCalcium homeostasis modulator 1Protein FAM26C

CALHM1 is targeted through ion channel blockade to prevent calcium-mediated excitotoxicity in conditions like stroke, or through potential channel activation to promote the clearance of amyloid-beta by facilitating the secretion of insulin-degrading enzyme in Alzheimer's disease.