BMPR2 and pulmonary arterial hypertension: Despite the high frequency of BMPR2 mutations in PAH patients, the disease penetrance rate is ~20% of the mutation carriers, suggesting that, in addition to BMPR2 mutations, other unidentified genetic, epigenetic, or environmental factors are involved in the development of the disease, potentially by decreasing BMPR2 expression and signaling activity below a specific threshold required to cause disease.