SEMA3C (semaphorin 3C) is a secreted signaling protein that functions as a key regulator of cellular migration and tissue remodeling across multiple pathological contexts. The protein binds to neuropilin receptors (NRP1 and NRP2) to activate downstream signaling pathways including AKT/Gli1/c-Myc and MAPK cascades 12. In cancer, SEMA3C promotes tumor progression through multiple mechanisms: it enhances hepatocellular carcinoma stemness and stromal remodeling via NRP1/ITGB1 signaling 1, facilitates colorectal cancer liver metastasis through NRP2-mediated MAPK activation 2, and drives esophageal adenocarcinoma progression when regulated by SOX4 3. SEMA3C also modulates immune cell function, regulating tumor-associated macrophage polarization through VNN1 to influence lung cancer invasion 4. In fibrotic diseases, SEMA3C exacerbates liver fibrosis by promoting hepatic stellate cell activation through NRP2 signaling 5 and contributes to diabetic kidney disease progression by promoting endothelial-mesenchymal transition 6. Additionally, SEMA3C increases vascular permeability and promotes acute kidney injury, making its genetic inactivation protective 7. A novel circRNA-encoded SEMA3C protein (319aa) triggers ferroptosis in gastric cancer through glutathione metabolism disruption 8.