IGSF6 (immunoglobulin superfamily member 6) is a transmembrane receptor belonging to the immunoglobulin superfamily, primarily expressed on immune cells including macrophages and dendritic cells 1. The gene spans approximately 10-12 kb with six exons and maps to chromosome 16-p12 1. IGSF6 functions as a cell surface signaling molecule involved in immune cell-cell interactions and recognition 2. Mechanistically, IGSF6 regulates anti-tumor macrophage activity, particularly M1 macrophage function. In lung adenocarcinoma, IGSF6 knockdown reduces M1 macrophage anti-tumor activity and promotes tumor progression 3. IGSF6 expression correlates positively with immune infiltration by anti-tumor immune cells, including CD8+ T cells and M1 macrophages 32. Clinical significance: IGSF6 exhibits diagnostic and prognostic value in multiple cancers. In lung adenocarcinoma, decreased IGSF6 expression associates with advanced TNM staging and poor survival 3. In mismatch repair-proficient colorectal cancer, high IGSF6 expression predicts improved sensitivity to immunotherapy and chemotherapy 2. In neuroblastoma, elevated IGSF6 correlates with improved event-free and overall survival 4. IGSF6 also appears relevant to inflammatory and metabolic diseases, identified as a hub gene shared between obesity and periodontitis pathogenesis 5. However, genetic variation in IGSF6 showed no association with inflammatory bowel disease susceptibility 6.