GDF2 (growth differentiation factor 2), also known as BMP9 (bone morphogenetic protein 9), functions as a potent circulating inhibitor of angiogenesis and regulator of vascular homeostasis 1. The protein signals through the type I activin receptor ACVRL1 and requires the TGF-beta coreceptor endoglin (ENG) for SMAD1 signaling in endothelial cells 2. GDF2 plays a critical role in the BMP signaling pathway and vascular development, with loss-of-function mutations causing hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations 12. Mutations in GDF2 are also associated with pulmonary arterial hypertension (PAH), where defective variants lead to reduced protein secretion and contribute to the pathogenesis of this rare vascular disorder 34. Beyond vascular functions, GDF2/BMP9 demonstrates protective effects in cardiac tissue by improving lymphatic drainage and promoting mitochondrial bioenergetics through DECR1-mediated pathways following myocardial infarction 5. The protein also exhibits anti-ferroptotic properties, protecting bone marrow mesenchymal stem cells from iron accumulation-induced damage through the USP10/FOXO1/GPX4 axis 6. Clinically, genetic testing for GDF2 variants is recommended for patients with HHT and PAH, as the gene has definitive evidence for causality in both conditions 47.