There are three primary genes associated with HHT: (1) endoglin (ENG) which encodes the endoglin protein, a non-intracellular co-receptor, (2) activin A receptor-like type 1 (ACVRL1) which encodes the activin receptor-like kinase-1 (ALK1), a serine–threonine intracellular receptor, and (3) suppressor of mothers against decapentaplegic (SMAD4) an intracellular transcription factor protein that aids transduction from the endoglin and ALK1 proteins toward gene expression. Here, SMAD4 is linked to hereditary hemorrhagic telangiectasia.