Increased Ca2+ leak through CALHM1 or CALHM2 in the SR/ER and inhibition of Ca2+ uptake into the SR/ER (Gallego-Sandin et al., 2011) can lead to store depletion and store-operated Ca2+ entry, another important pathway to increase [Ca2+]cyt required for or involved in PASMC proliferation and migration and pulmonary vascular remodeling in PAH/PH (Sweeney et al., 2002; Yu et al., 2003; Song et al., 2018). Here, CALHM1 is linked to pulmonary arterial hypertension.