SEMA3G (semaphorin 3G) is a secreted signaling protein with context-dependent functions across multiple physiological systems. Structurally, it acts as a ligand for neuropilin receptors (NRP1 and NRP2) and plexin co-receptors, mediating cell-cell communication through paracrine signaling 1. In vascular biology, endothelial-derived SEMA3G plays a protective role in ischemic retinopathies by coordinating β-catenin-dependent vascular remodeling through NRP2/PlexinD1 signaling under hypoxic conditions 1. However, in diabetic vascular disease, SEMA3G promotes pathological smooth muscle cell proliferation and migration via NRP2/PlexinA1-mediated YAP activation 2, and its upregulation by SETD7-dependent chr3 remodeling impairs angiogenic responses 3. In the central nervous system, endothelial SEMA3G functions as a vascular-derived synaptic organizer, enhancing excitatory synapse density and hippocampal-dependent memory through NRP2/PlexinA4/Rac1 signaling 4. During neural development, SEMA3G expression is upregulated by developmental toxins like dioxin, potentially disrupting axonal projections 5. In cancer, SEMA3G establishes an immunosuppressive microenvironment by suppressing CD8+ T-cell cytotoxicity via NRP1 signaling 6, while in glioblastoma, endothelial-derived SEMA3G suppresses glioblastoma stem cells through NRP2/PlexinA1-mediated c-Myc degradation 7. SEMA3G also mediates BMP9-induced anti-angiogenic effects by inhibiting VEGFR2 phosphorylation 8.