The majority of individuals fulfilling the clinical diagnostic criteria for HHT harbor pathogenic variants in four known genes involved in the transforming growth factor-beta pathway [i.e., Endoglin (ENG), Activin Receptor Like 1 (ACVRL1 or ALK1), SMAD family member 4 (SMAD4), Growth Differentiation Factor 2 (GDF2 or BMP9)] [24]. Here, SMAD4 is linked to hereditary hemorrhagic telangiectasia.