ENG and ALK1 are cell-surface transmembrane receptors involved in TGF-β1 and BMP signaling pathways that can activate pSMAD1/5/8, and impairment or mutations of ENG and or ALK1 signaling can lead to vascular malformations associated with HHT disease (21). This evidence concerns the gene ACVRL1 and hereditary hemorrhagic telangiectasia.