The concern that the same ligand might have opposite effects is illustrated by contradicting reports showing that genetic deletion or pharmacological inactivation of BMP9 protects rodents from experimental PH [22], while a case study associates a homozygous nonsense mutation in GDF2 (encoding for BMP9) with the development of PAH in infants [23], and BMPR2 loss-of-function mutations are known to alter the tissue microenvironment [24]. The gene discussed is GDF2; the disease is pulmonary arterial hypertension.