All three identified genes associated with HHT are constituents of signal transduction of TGF-β family members (ENG: type III receptor; ALK1: type I receptor; SMAD4: intracellular mediator) [4–6]; thus, HHT has been considered a disease caused by defects in the signaling of a TGF-β family member(s). Here, SMAD4 is linked to hereditary hemorrhagic telangiectasia.