IRF1 (interferon regulatory factor 1) is a transcriptional regulator that plays essential roles in immune responses and cellular homeostasis. As a primary function, IRF1 acts as both a transcriptional activator and repressor, binding to interferon-stimulated response elements (ISREs) in target gene promoters to regulate diverse cellular processes including antiviral responses, inflammation, cell cycle control, and apoptosis 12. Mechanistically, IRF1 functions through multiple pathways: it regulates PD-L1 expression via phase separation with KAT8, forming biomolecular condensates that promote transcriptional activation 3, and controls interferon-gamma-induced PD-L1/PD-L2 expression in the JAK-STAT-IRF1 signaling axis 1. IRF1 is particularly crucial for IFN-γ-dependent macrophagic immunity against mycobacteria, with deficiency leading to severe mycobacterial infections while preserving antiviral immunity 2. Disease relevance includes its role as a tumor suppressor, where it promotes antigen presentation and anti-tumor immunity 4, and its involvement in inflammatory responses where IL-10 suppresses IRF1 activity to control excessive inflammation 5. Clinically, IRF1 represents a potential therapeutic target, with inhibitors showing promise in treating immune disorders and its activity being modulated by various cellular stresses including radiation and viral infections 6.