Although BMPR2 mutations are major predisposing factors for idiopathic (15–40%) and heritable (60–80%) PAH, less common or rare mutations in other genes encoding key members of the Smad1/5/8 signaling pathway, including ALK1, GDF2 (BMP9) and BMP10 have been identified, underlining the critical role of this pathway in PAH [15]. This evidence concerns the gene ACVRL1 and pulmonary arterial hypertension.