IFITM3 (interferon-induced transmembrane protein 3) is a multifunctional antiviral protein that serves as a critical effector of the type I interferon response. IFITM3 primarily functions to inhibit viral entry by disrupting membrane fusion processes, specifically by inducing local lipid sorting that stabilizes hemifusion and prevents fusion pore formation 1. This mechanism effectively blocks entry of diverse viruses including influenza, coronaviruses, and other enveloped viruses 2. Beyond its antiviral role, IFITM3 modulates γ-secretase activity in neurons and astrocytes, leading to increased amyloid-β production when upregulated by inflammatory cytokines 3. In cerebrovascular endothelial cells, IFITM3 enhances Aβ generation through regulation of BACE1 and γ-secretase, creating a pathological cycle in Alzheimer's disease 4. IFITM3 also regulates immune responses by controlling MHC-I expression through NLRC5 upregulation, thereby enhancing antigen presentation and CD8+ T-cell infiltration 5. Disease relevance includes Alzheimer's pathogenesis, where targeting cerebrovascular IFITM3 shows therapeutic promise 4, and cancer immunotherapy, where IFITM3 expression predicts anti-PD-1/PD-L1 therapy efficacy in small cell lung cancer 5. Natural genetic variation in IFITM3 expression significantly influences individual susceptibility to viral infections, including Zika virus 6.