SEMA7A (semaphorin 7A) is a GPI-anchored glycoprotein functioning as a neuroimmune guidance molecule with critical roles in inflammation, immunity, and metabolic homeostasis 1. Primary function involves integrin-mediated signaling through β1-integrin and plexinC1 receptors, promoting cell migration, focal adhesion formation, and FAK/MAPK activation 1. SEMA7A orchestrates macrophage metabolic remodeling and polarization toward the pro-resolving M2 phenotype, facilitating inflammation resolution by activating mTOR and AKT2 pathways and promoting specialized pro-resolving lipid mediator synthesis 2. The protein regulates lipid metabolism in hepatocytes and adipocytes through integrin β1-PKCα signaling, suppressing adipogenesis and lipogenesis 34. Pathologically, SEMA7A mutations (R148W) cause progressive familial intrahepatic cholestasis by reducing bile acid transporter expression (BSEP, MRP2) 5. In cancer, aberrant N-glycosylation of SEMA7A—catalyzed by FUT8—promotes head and neck squamous cell carcinoma progression by inducing CD8+ T cell exhaustion and immunosuppression 6. SEMA7A elevation in breast cancer similarly drives PD-L1-mediated immunosuppression, making SEMA7A antagonism a potential therapeutic strategy 7. SEMA7A serves as a diagnostic biomarker for neurosyphilis in cerebrospinal fluid 8, highlighting its utility in inflammatory disease assessment and therapeutic targeting.