IFIT5 is an interferon-induced RNA-binding protein that serves as a critical component of innate antiviral immunity 1. Its primary function involves recognizing viral RNA signatures through selective binding of single-stranded RNAs bearing 5'-triphosphate groups (PPP-RNA), which lack 2'-O-methylation and distinguish viral from self mRNAs 2. IFIT5 exhibits broad RNA recognition specificity, binding precursor and processed tRNAs, poly-U-tailed tRNA fragments, and other RNA polymerase III transcripts in a non-sequence-specific manner 1. The protein's unique TPR eddy fold structure, formed by eight tetratricopeptide repeats, creates an RNA-binding cleft essential for recognition 2. Additionally, IFIT5 recognizes AT-rich double-stranded DNA and positively regulates IKK-NFKB signaling by promoting IKK recruitment to MAP3K7, amplifying innate immune responses 3. Beyond antiviral defense, IFIT5 expression is dysregulated in autoimmune conditions like systemic lupus erythematosus, where it is downregulated in CD4+ T cells 4. In cancer biology, IFIT5 acts as an oncogene in bladder cancer, promoting epithelial-mesenchymal transition and metastasis through miR-99a-mediated ICAM1 upregulation 5. IFIT5 localizes to actin-rich protrusions at the apical cell surface, colocalizing with RIG-I for coordinated antiviral sensing 2.