Ifit2, also known as ISG54 (Interferon-stimulated gene 54), is a member of the interferon-stimulated gene (ISG) family. It plays essential roles in antiviral and antitumor activities. It is involved in multiple biological processes such as immune responses, cell adhesion, and oxidative stress through pathways like NF-κB, Wnt, TNF, and HIF-1 [2]. The study of Ifit2-deficient mouse models has been crucial for understanding its functions.

In Ifit2-deficient mice infected with neurotropic murine-β-coronavirus RSA59, there was extensive viral spread throughout the spinal cord gray and white matter, impaired CD4+ T and CD8+ T cell infiltration, and severe demyelination in the chronic phase, highlighting Ifit2's role in promoting acute neuroinflammation and limiting chronic demyelination [3,4]. In oral cancer, IFIT2 depletion promotes cancer stem cell-like phenotypes, as IFIT2 knockdown cells overexpress ABCG2 and CD44, downregulate CD24, and show increased sphere formation ability [1]. In an atherosclerotic model, IFIT2 knockdown in APOE-/-mice fed a high-fat diet led to reduced plasma lipid levels, plaque area, immune infiltration, iron retention, and lipid accumulation, and in vitro, it alleviated ox-LDL-induced iron retention and lipid accumulation in foamy macrophages [2].

In conclusion, Ifit2 is important in antiviral defense, especially against neurotropic viruses, and in preventing severe chronic demyelination. In cancer, it seems to act as a suppressor of cancer stem-like phenotypes. In atherosclerosis, it mediates iron retention and cholesterol efflux. The use of Ifit2-deficient mouse models has significantly enhanced our understanding of its functions in these disease areas.