SERINC3 is a multipass transmembrane protein that functions as a host restriction factor against lentiviruses, particularly HIV-1 1. It acts as a non-ATP-dependent phospholipid scramblase, catalyzing bidirectional flipping of phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine across viral membranes 2. When incorporated into HIV-1 virions, SERINC3 disrupts normal membrane asymmetry, exposing phosphatidylserine on the viral surface and altering Env conformation, which substantially reduces viral infectivity 2. This antiviral activity is conserved across mammalian species including rodents and lagomorphs 3. HIV-1 counteracts SERINC3 restriction through its Nef accessory protein, which prevents SERINC3 incorporation into virions via clathrin-dependent internalization, an interaction that varies among HIV-1 subtypes 14. Silencing both SERINC3 and SERINC5 increases nef-deficient HIV-1 infectivity more than 100-fold, highlighting their combined restriction capacity 1. Beyond antiviral immunity, SERINC3 has been identified as a potential biomarker in coronary artery disease pathophysiology within endoplasmic reticulum stress pathways, though this role requires further characterization 5. The SERINC3-Nef antagonism represents a therapeutic target for HIV/AIDS intervention 6.