Ifit2, also known as IFN-stimulated gene 54 (ISG54), is a member of the interferon-stimulated gene (ISG) family. It plays crucial roles in antiviral and antitumor activities, and is involved in pathways such as immune responses, cell adhesion, and oxidative stress [1,3,7]. Genetic models, especially knockout mouse models, are valuable for studying its functions.

In Ifit2-deficient mice infected with murine-β -coronavirus RSA59, there is extensive viral spread throughout the spinal cord gray and white matter, along with impaired microglial activation, T cell infiltration, and severe chronic demyelination, highlighting Ifit2's role in promoting acute neuroinflammation and limiting chronic demyelination [4]. In oral cancer, IFIT2 depletion promotes cancer stem-cell-like phenotypes, and in oral squamous cell carcinoma, IFIT2-depleted metastatic cells induce muscle atrophy and cancer cachexia in mice [2,5]. In esophageal cancer, decreased IFIT2 expression increases cell viability, invasion, and migration, and is related to epithelial-to-mesenchymal transition [6]. In renal cancer, higher IFIT2 expression is associated with better overall survival [7]. In osteosarcoma, L3MBTL2 acts as a tumor suppressor by transcriptionally repressing IFIT2 [8].

In conclusion, Ifit2 is essential in antiviral defense and tumor-related processes. Studies using Ifit2 knockout mouse models have significantly advanced our understanding of its role in neurological diseases like viral-induced demyelination, as well as in various cancers, including oral, esophageal, renal, and osteosarcoma.