AGGF1 (angiogenic factor with G-patch and FHA domains 1) is a multifunctional angiogenic factor that promotes endothelial cell proliferation and vasculogenesis 1. The protein acts as a key regulator of vascular development through multiple signaling pathways: it enhances hemangioblast specification via the mTOR-S6K-ERK1/2 axis upstream of npas4l 2, coordinates TNFSF12/FN14 signaling to induce retinal angiogenesis 1, and regulates alternative RNA splicing through formation of AGGF1-coated paraspeckles 3. Beyond angiogenesis, AGGF1 exhibits protective roles in non-vascular tissues: it attenuates thoracic aortic aneurysm progression by enhancing integrin α7-mediated inhibition of TGF-β1 maturation 4, and ameliorates skeletal muscle atrophy by inhibiting MuRF1 expression through the AGGF1-TWEAK/Fn14-NF-κB pathway 5. Clinically, AGGF1 elevation is associated with pathological angiogenesis in diabetic retinopathy 1, and its aberrant expression correlates with poor prognosis in esophageal carcinoma 6 and hepatocellular carcinoma 7. AGGF1 dysfunction—from gain-of-function mutations causing Klippel-Trenaunay syndrome to loss-of-function mutations in cancer 3—underscores its importance as both a therapeutic target and potential protein therapeutic agent.