Activin A receptor-like kinase 1 (ALK1)

Activin A receptor-like kinase 1 (ALK1), encoded by the ACVRL1 gene, is a type I cell-surface receptor belonging to the transforming growth factor-beta (TGF-beta) superfamily of proteins. It is predominantly expressed in vascular endothelial cells where it plays a critical role in regulating angiogenesis and maintaining vascular integrity by signaling through the SMAD1/5/8 pathway upon binding ligands such as BMP9 and BMP10 (UniProt P37023; PubMed: 11574486). Mutations in the ACVRL1 gene are the primary cause of Hereditary Hemorrhagic Telangiectasia type 2 (HHT2), a condition characterized by vascular malformations and chronic bleeding (PubMed: 28530676). In oncology, ALK1 is targeted to inhibit tumor-associated angiogenesis, as its signaling promotes the maturation of new blood vessels that sustain tumor growth. Therapeutic strategies include the use of ALK1-Fc fusion proteins like dalantercept, which act as ligand traps to prevent receptor activation, although clinical challenges include managing cardiovascular side effects such as hypertension and fluid retention (PubMed: 24947923).

Other names

ACVRL1Serine/threonine-protein kinase receptor R3SKR3HHT2ORW2TGF-B superfamily receptor type I

Drugs targeting ALK1 typically act as ligand traps (e.g., ALK1-Fc fusion proteins) that sequester circulating ligands like BMP9 and BMP10, or as multi-kinase inhibitors that block the intracellular kinase domain to inhibit downstream SMAD1/5/8 signaling pathways involved in angiogenesis.