The notion that HHT is caused by loss-of-function mutations was strengthened by studies in mouse29 and zebrafish30 models showing that ALK1 or endoglin deficiency, or injection of ALK1 extracellular domain-derived ligand trap (ALK1-Fc), led to vascular hyperproliferation and AVMs. Here, ACVRL1 is linked to hereditary hemorrhagic telangiectasia.