IFI44 (interferon-induced protein 44) is an interferon-stimulated gene that functions as a key regulator in immune response and viral defense mechanisms. The protein aggregates to form microtubular structures and exhibits protein-binding capabilities within the cytosol [UniProt annotation]. Mechanistically, IFI44 expression is regulated by interferon signaling pathways, particularly through IRF1, JAK1, TYK2, and STAT1 activation, with both type I interferons (IFNα/IFNβ) and IRF4 modulating its expression 12. Clinically, IFI44 serves as a diagnostic and prognostic biomarker across multiple autoimmune and malignant conditions. In systemic lupus erythematosus (SLE) and lupus nephritis (LN), IFI44 is significantly upregulated and correlates with disease severity markers including elevated ESR, anti-CCP, and serum creatinine, while inversely correlating with complement C3 and eGFR 34. IFI44 demonstrates superior diagnostic sensitivity for rheumatoid arthritis compared to IRF4 1 and is confirmed as a hub gene in insomnia-associated autoimmune uveitis 5. In head and neck squamous cell carcinoma, ACSL4-mediated upregulation of IFI44 promotes cell proliferation and invasiveness through enhanced interferon signaling 2. In glioma, high IFI44 expression associates with poor prognosis, higher tumor grade, and immune-suppressive microenvironment enrichment with increased checkpoint molecule expression 6. Additionally, intestinal IFNα4-induced IFI44 expression contributes to pulmonary hypertension development via CD8 T-cell TRAIL upregulation 7, and IFI44 serves as a diagnostic biomarker for Sjögren's syndrome with strong discriminatory power 8.