The increased cytosolic [Ca2+] due to Ca2+ influx through CALHM1/2 and increased extracellular [ATP] due to ATP transportation through upregulated CALHM1/2 stimulate PASMC proliferation contributing to the development and progression of pulmonary vascular remodeling in patients with PAH and animals with experimental PH. Here, CALHM1 is linked to pulmonary arterial hypertension.