Downregulated ENG expression disrupted the ALK1- and ALK5-dependent TGFβ pathways, disorganized the cytoskeleton, and led to a failure to form cord-like structures, thus leading to fragility in the small vessels and bleeding after injuries, which explains the clinical symptoms of the HHT disease. Here, TGFBR1 is linked to hereditary hemorrhagic telangiectasia.