ACVRL1 encodes activin receptor-like kinase 1 (ALK1), a type I serine/threonine kinase receptor essential for bone morphogenetic protein (BMP) signaling in vascular development 1. Upon ligand binding (BMP9/BMP10), ACVRL1 forms a receptor complex with type II receptors, leading to phosphorylation and activation of receptor-regulated SMADs (primarily Smad1/5/9), which regulate transcription of angiogenic genes 2. ACVRL1 functions as a critical negative regulator of endothelial cell migration and proliferation, promoting vascular quiescence and normal blood vessel morphogenesis 3. ACVRL1 loss-of-function variants cause hereditary hemorrhagic telangiectasia type 2 (HHT2), accounting for approximately 52% of HHT cases among clinically diagnosed patients 4. HHT is characterized by mucocutaneous telangiectasias causing recurrent epistaxis and gastrointestinal bleeding, and arteriovenous malformations (AVMs) in lungs, liver, and central nervous system 1. ALK1 deficiency leads to pathological upregulation of VEGFR2/PI3K/AKT signaling and elevated PIEZO1 mechanosensitive signaling, promoting abnormal endothelial cell proliferation and AVM formation 3. ACVRL1 holds definitive evidence for PAH causality 5. Management focuses on screening and treatment of AVMs, bleeding control, and iron supplementation, with emerging antiangiogenic therapies under investigation 1.