Based on limited published evidence, CALHM5 is a calcium homeostasis modulator that assembles into large pore channels with gating likely regulated by membrane lipids. The protein functions as a plasma membrane ion channel with monoatomic cation channel activity 1. CALHM5 forms an undecamer structure with four transmembrane helices and intracellular domains 1. In smooth muscle cells, CALHM5 regulates calcium homeostasis and blood vessel contractility by modulating L-type calcium channel expression 2. Dysfunction has been associated with neurological pathologies including Alzheimer's disease and depression 1, while downregulation in aortic tissue may protect against aneurysm development 2.