Activin A receptor type II-like 1 (ACVRL1)

Activin A receptor type II-like 1 (ACVRL1), also known as activin receptor-like kinase 1 or ALK1, is a type I cell-surface serine/threonine kinase receptor and member of the transforming growth factor-beta (TGF-β) superfamily[1][3][5]. Predominantly expressed in endothelial cells, ACVRL1 plays a central role in vascular development, angiogenesis, and the maintenance of vessel homeostasis[1][3]. ACVRL1 mediates signaling mainly via binding to bone morphogenetic protein 9 (BMP9) and BMP10, leading to phosphorylation of SMAD1/5/8 proteins and influencing endothelial cell proliferation, migration, and vascular patterning[1]. Mutations in ACVRL1 are causative for hereditary hemorrhagic telangiectasia type 2 (HHT2), a genetic disorder marked by abnormal blood vessel formation and bleeding tendencies, as well as other vascular malformations such as pulmonary arterial hypertension[5][3]. ACVRL1 is considered a promising therapeutic target, especially in conditions marked by dysregulated angiogenesis, such as certain cancers or vascular anomalies. Therapies under investigation include antibodies, ligand traps, or fusion proteins that inhibit ligand binding or downstream signaling via the ACVRL1 pathway[1].

Other names

Activin receptor-like kinase 1ALK1ALK-1ACVRLK1Serine/threonine-protein kinase receptor R3HHT2HHTSKR3TSR-IORW2TGF-B superfamily receptor type I

Inhibition of ligand binding to ALK1 (using decoy receptors or fusion proteins to sequester BMP9/10); Blockade of downstream signaling (e.g., SMAD phosphorylation inhibition).