Ifitm3, short for Interferon-induced transmembrane protein 3, is a protein encoded by this gene. It plays a crucial role in the innate immune response, especially in inhibiting the entry of numerous viruses. It localizes in the endosomal-lysosomal system and affects virus fusion with target cell membranes [1,4]. It is also associated with interferon signaling as part of the inflammatory response [3]. Genetic models, such as gene knockout in mice, can be used to study its functions.

In a 5xFAD transgenic mouse model of early amyloid deposition, knockout of Ifitm3 reduces γ-secretase activity and the formation of amyloid plaques. This shows that Ifitm3, when expressed, binds to γ-secretase and upregulates its activity, increasing the production of amyloid-β, thus contributing to Alzheimer's disease pathogenesis [2,7]. In glioblastoma, loss-of-function experiments using shRNAs targeting Ifitm3 in primary glioblastoma stem cells (GSCs) demonstrated that Ifitm3 promotes GSC-mediated angiogenesis. Ifitm3 causes activation of Jak2/STAT3 signaling and leads to robust secretion of bFGF into the tumor environment [5]. In Tregs, depletion of Ifitm3 enhances the translation and phosphorylation of STAT1, blunting tumor growth by strengthening the tumor-killing response and displaying a Th1-like Treg phenotype [6].

In conclusion, Ifitm3 has essential functions in antiviral defense, and its dysregulation is associated with Alzheimer's disease, glioblastoma, and tumor-infiltrating Tregs. Gene knockout and loss-of-function experiments in mouse models have been instrumental in revealing its role in these disease conditions, helping to understand the underlying molecular mechanisms and potentially guiding new therapeutic strategies.