ACVRL1 and hereditary hemorrhagic telangiectasia: This clearly indicates that Endoglin is particularly important under conditions, in which ALK1 or its ligands are limited (e.g., genetically primed ALK1 or BMP9/10 deficiencies which lead to severe vascular pathologies like hereditary hemorrhagic telangiectasia (HHT) or pulmonary arterial hypertension (PAH) [50–52]), while it appears to adopt a negative regulatory role for phospho-SMAD1/5 signaling upon EC adaptation to flow.