SERINC5 (serine incorporator 5) functions as a restriction factor that inhibits retroviral and some non-retroviral infections by disrupting viral membrane fusion processes 12. As a multipass transmembrane protein, SERINC5 becomes incorporated into viral particles during assembly and blocks viral core penetration into target cells by impairing the fusion between viral and cellular membranes after initial receptor binding 2. The protein functions as a non-ATP-dependent phospholipid scramblase, transporting phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine bidirectionally across membranes, which disrupts membrane asymmetry and alters viral envelope conformations 3. SERINC5 restricts multiple viruses including HIV-1, murine leukemia virus, equine infectious anemia virus, and influenza A virus, with viral sensitivity depending on envelope glycosylation patterns 14. HIV-1 and other retroviruses have evolved countermeasures through accessory proteins (Nef, glycoGag, S2) that target SERINC5 for endosomal degradation 15. Beyond direct antiviral activity, SERINC5 enhances viral neutralization by antibodies and modulates innate immune signaling pathways 67. The protein's restriction activity significantly contributes to overall antiviral host defense mechanisms 5.