CALHM1-mediated activation of ERK1/2 signaling, or Ca2+ activation of ERK1/2 signaling by Ca2+ influx through CALHM1 in the plasma membrane and Ca2+ mobilization through CALHM1 in the SR/ER, plays an important role in the regulation of cell proliferation and gene expression (Morrell et al., 2009) and the development of pulmonary vascular remodeling in patients with PAH and animals with experimental PH (Awad et al., 2016). The gene discussed is MAPK3; the disease is pulmonary arterial hypertension.