Based on the fact that ENG, ALK1, and SMAD4 are receptors or intracellular mediator of transforming growth factor-β (TGF-β) family signals, it has been postulated that impaired signaling of TGF-β family member(s) would be an important pathological mechanism of HHT. The gene discussed is ACVRL1; the disease is hereditary hemorrhagic telangiectasia.