The in vivo importance of Eng for signaling of individual ligands of the TGF-β family becomes evident by the human disease hereditary hemorrhagic telangiectasia type-1 (HHT-1) caused by Eng haploinsufficiency/and dominant negative effects caused by truncation, nonsense and missense mutants of Eng affecting endothelial cell biology [23,24]. This evidence concerns the gene TGFB1 and telangiectasia, hereditary hemorrhagic, type 1.