IFIT3 (interferon-induced protein with tetratricopeptide repeats 3) is an interferon-stimulated gene encoding a multifunctional antiviral and immunoregulatory protein. Mechanistically, IFIT3 enhances host antiviral responses by bridging TBK1 to MAVS, leading to TBK1 and IRF3 phosphorylation and subsequent antiviral gene transcription 1. IFIT3 also activates the STING pathway to restrict viral replication, including DNA viruses like adenovirus, through mechanisms independent of viral pathogen-associated molecular patterns 1. As an RNA-binding protein, IFIT3 modulates IFIT1 stability and enhances its specificity for cap 0 RNA recognition, thereby restricting viruses lacking 2'-O methylation 2. Beyond antiviral immunity, IFIT3 exhibits antiproliferative activity by upregulating cell cycle inhibitors CDKN1A/p21 and CDKN1B/p27 3. IFIT3 sequesters COPS5 in the cytoplasm, increasing nuclear p27 retention, while downregulating MYC to boost p21 expression. In cancer contexts, IFIT3 shows emerging significance: it is upregulated in metastatic esophageal squamous cell carcinoma lymph nodes 4, downregulated in PD-1+ colorectal cancer cells treated with nivolumab 5, and essential for pyroptosis induction in myeloma and leukemia 6. Mpox virus antagonizes IFIT3 expression via STAT2 sequestration 7, highlighting its importance as a viral restriction factor. These diverse roles position IFIT3 as a potential biomarker for disease diagnosis and therapeutic targeting 3.