VEGFB (vascular endothelial growth factor B) is a member of the VEGF family that exhibits complex and context-dependent roles in angiogenesis and metabolism 1. Unlike other VEGF family members, VEGFB demonstrates an unexpected anti-angiogenic function under specific conditions by binding to FGFR1, forming FGFR1/VEGFR1 complexes, and inhibiting FGF2-driven angiogenesis through suppression of Erk activation 2. This anti-angiogenic property prevents excessive vessel formation when FGF2/FGFR1 levels are high. Beyond vascular regulation, VEGFB plays significant metabolic roles, particularly in insulin signaling. VEGFB ameliorates insulin resistance in non-alcoholic fatty liver disease (NAFLD) by activating the PI3K/AKT pathway through VEGFR1, promoting glucose uptake via GLUT2 upregulation, and maintaining glucose homeostasis 3. In neuroinflammation, microglial VEGFB triggers FLT-1 signaling in astrocytes and exacerbates experimental autoimmune encephalomyelitis 4. VEGFB also promotes angiogenesis in fracture healing and demonstrates protective effects against UVB-induced photoaging 56. Clinical relevance extends to neurodegenerative diseases, where plasma VEGFB levels are associated with multiple sclerosis and blood-brain barrier integrity through Mendelian randomization studies 7. These findings highlight VEGFB's multifaceted roles beyond traditional angiogenic functions.