Gremlin-1 was found to play vital roles in PAH associated with congenital heart disease (systemic-to-pulmonary shunts), which does not typically arise from BMPR2 mutation; in this case, gremlin-1 could help to explain reduced BMPRII–SMAD1/5/8 pathway activity in the presence of intact BMPR263. Here, BMPR2 is linked to congenital heart disease.