The most recent breakthrough in PAH therapy is sotatercept, an activin receptor type IIA fusion protein (IIA-Fc) that restores the imbalance between overpromoted Smad2/3 pro-proliferative signaling and Smad1/5/8 antiproliferative signaling in PAH patients [3]. Here, SMAD1 is linked to pulmonary arterial hypertension.