BMPR2 and idiopathic pulmonary arterial hypertension: Most cases of HPAH (>70%) and some IPAH cases (~20%) caused by mutations in the BMPR2 are associated with a down-regulation of BMPR2 expression and weakened SMAD1/5 signaling, causing major phenotypic abnormalities and vascular lesions that are predominantly in the lungs [4,11,12].