The gene for the type 2 receptor for the bone morphogenic pathway, BMPR2, is mutated in a large majority of familial pulmonary arterial hypertension (PAH),. However, the mechanisms linking BMPR2 mutation to disease remain obscure. BMPR2 potentially signals through multiple immediate downstream pathways, including Smad, MAPK, LIM domain kinase 1 (LIMK) and dynein, light chain, Tctex-type 1 (TCTEX), v-src sarcoma viral oncogene homolog (SRC), and nuclear factor kappa-B (NFkB). Functional consequences of BMPR2 mutation, largely ascertained from animal models, include a shift from contractile to synthetic phenotype in smooth muscle, probably downstream of Smad signal; alterations in expression of actin organization related genes, possibly related to focal adhesions; alterations in cytokines and inflammatory cell recruitment; increased proliferation and apoptosis; and increased collagen and matrix. A synthesis of the available data suggests that the normal role of BMPR2 in adult animals is to assist in injury repair. BMPR2 is suppressed in injured tissue, which facilitates inflammatory response, shift to a synthetic cellular phenotype, and alterations in migration or permeability of cells in the vascular wall. We thus hypothesize that BMPR2 mutation thus leads to an impaired ability to terminate the injury repair process, leading to strong predisposition to PAH.