The significance of the BMP9–ALK-1/BMPR2-mediated signal in endothelial cell is supported by the causal mutations identified in pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia patients in the ACVRL1 and GDF2 genes, which encode ALK-1 and BMP9, respectively70,71. Here, ACVRL1 is linked to pulmonary arterial hypertension.