EPSTI1 (epithelial-stromal interaction 1) is an interferon-stimulated gene located on chromosome 13 that plays multifaceted roles in immune regulation and disease pathogenesis. Primary Function: EPSTI1 functions as an immunomodulatory factor involved in M1 macrophage polarization and osteoclast differentiation 1. Mechanism: EPSTI1 regulates immune responses through multiple signaling pathways, including PKR/NF-κB signaling in osteoclastogenesis 1 and IFN-β-mediated HLA-A expression in myoblasts 2. The gene positively correlates with antigen presentation, chemokine signaling, and interferon pathways 2. Disease Relevance: EPSTI1 is significantly upregulated in systemic lupus erythematosus (SLE), where it correlates with disease activity (SLEDAI score) and T cell activation markers 3. In osteoporosis, EPSTI1 expression increases in osteoclasts and promotes bone resorption via PKR/NF-κB signaling 1. EPSTI1 is upregulated in dermatomyositis muscle tissues and promotes muscle inflammation 2. Clinical Significance: EPSTI1 serves as a potential diagnostic and prognostic biomarker for SLE 3 and stage III colon cancer, where higher EPSTI1 correlates with improved relapse-free survival and enhanced M1 macrophage infiltration 4. However, EPSTI1 shows contrasting effects in squamous cell carcinomas, functioning oncogenically in oral but suppressively in lung cancers 5, suggesting context-dependent roles in malignancy.