The TGFBR2 and BMPR-II receptors act as central regulators of downstream SMAD signaling, whose dysregulation is closely linked to PAH pathogenesis, particularly through impaired BMP-SMAD1/5/8 activity and excessive activin–SMAD2/3 responses leading to vascular remodeling [65,66,67]. This evidence concerns the gene SMAD1 and pulmonary arterial hypertension.