IRF9 is a transcription factor essential for type I interferon-mediated antiviral immunity. Upon type I IFN (IFN-α/β) binding to cell surface receptors, Jak kinases TYK2 and JAK1 are activated, phosphorylating STAT1 and STAT2 1. IRF9 associates with phosphorylated STAT1:STAT2 to form the ISGF3 transcription factor complex, which translocates to the nucleus and binds interferon-stimulated response elements (ISREs) to activate antiviral genes 2. Beyond canonical JAK-STAT signaling, IRF9 undergoes posttranslational modifications regulating its function; L-lactylation of IRF9 mediated by AARS1 enhances type I interferon signaling by promoting IRF9-STAT2 interaction and strengthening antiviral responses, while viral-induced SIRT1-mediated delactylation suppresses immunity 3. IRF9 plays broader roles in immune regulation: it functions as a transcription factor in interferon-stimulated gene expression in systemic lupus erythematosus 4 and is involved in calcium signaling pathway regulation during ischemic stroke pathogenesis 5. IRF9 also participates in macrophage polarization through the PI3K/AKT pathway in lung adenocarcinoma progression 6. Dysregulation of IRF9 is associated with immunodeficiency and autoimmune conditions, establishing its clinical significance in both antiviral defense and immune homeostasis.