Endoglin (ENG) is a vascular endothelium glycoprotein essential for angiogenesis and vascular integrity. ENG functions as a TGF-β coreceptor, regulating the TGF-β/BMP signaling cascade that activates SMAD transcription factors 123. Specifically, ENG is required for GDF2/BMP9 signaling through SMAD1 and modulates TGFB1 signaling through SMAD3 in endothelial cells 13. Beyond angiogenesis, ENG regulates vascular endothelial cell migration and may control endothelial cell shape changes in response to blood flow, driving vascular remodeling and morphology establishment 4. ENG is critical for normal adult vasculature structure and integrity 5. Clinically, ENG mutations cause hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations 67. ENG variants account for approximately 44% of HHT cases meeting Curaçao diagnostic criteria 8. ENG mutations also associate with pulmonary arterial hypertension severity, with pathogenic mutations correlating with earlier disease onset 9. Additionally, elevated endothelium-derived ENG delivered via extracellular vesicles triggers astrocyte reactivity and neuroinflammation in Alzheimer's disease pathogenesis 10. ENG's selective expression on tumor vasculature makes it an attractive target for vascular-targeting antiangiogenic cancer therapy 11.