ALK1

ALK1 (activin receptor-like kinase 1), encoded by ACVRL1, is an endothelial-enriched transmembrane serine/threonine kinase receptor within the transforming growth factor-β (TGF-β) receptor superfamily that plays a central role in vascular development, endothelial homeostasis, and angiogenic regulation^[1][2][3]. Mechanistically, ALK1 functions as a type I receptor that responds primarily to the circulating ligands BMP9 and BMP10, activating downstream SMAD1/5/8-dependent transcriptional programs that regulate endothelial behavior and vascular quiescence^[4][5][6]. Continuous BMP10-mediated ALK1 signaling is required for vascular maintenance, and disruption of this pathway leads to arteriovenous malformations, highlighting its importance in endothelial integrity^[4]. Consistent with this function, loss-of-function mutations in ACVRL1 are a major cause of hereditary hemorrhagic telangiectasia type 2 (HHT2), a vascular disorder characterized by abnormal artery-vein connections and pathological angiogenesis^[1][4][7]. ALK1 mutations have also been associated with pulmonary arterial hypertension and altered endothelial transcriptional responses to BMP9 and BMP10 stimulation. Compared with related TGF-β family type I receptors, ALK1 exhibits marked endothelial-cell specificity, particularly in arterial endothelial cells, distinguishing its biological role from more broadly expressed receptor kinases^[1][2]. For experimental applications, recombinant BMP9 and BMP10 are widely used to activate ALK1 signaling, whereas ALK1-targeting antagonists and ligand-trap strategies have been investigated to modulate angiogenesis and vascular remodeling in preclinical disease models, including cancer-associated angiogenesis^[6][8][9].