ICAM2 (intercellular adhesion molecule 2) is a cell adhesion molecule that functions as a receptor ligand for the integrin LFA-1/ITGAL:ITGB2 on resting leukocytes, mediating leukocyte cell-cell adhesion essential for immune surveillance 1. ICAM2 also serves as a ligand for dendritic cell CD209 receptor, promoting transendothelial migration of dendritic cell precursors from blood into peripheral and lymphoid tissues 2. Beyond classical immune functions, ICAM2 exhibits context-dependent roles in disease pathology. In early pancreatic tumorigenesis, ICAM2 expression promotes anti-tumor immune responses by facilitating dendritic cell infiltration and cytotoxic T-cell-mediated cytolysis 3. Conversely, in gastric cancer, ICAM2 acts as a tumor suppressor—downregulation of ICAM2 correlates with chemoresistance through TGF-β/Smad pathway activation and M2 macrophage polarization 4. ICAM2 also mediates blood-cerebrospinal fluid barrier adhesion and trans-barrier migration in leptomeningeal metastasis through interactions with ICAM1 5. Recent metabolic studies reveal ICAM2 involvement in glucose homeostasis through interactions with bacterial protein P9 6, and elevated ICAM2 serves as a serum biomarker for proliferative lupus nephritis activity 7. These findings establish ICAM2 as a multifunctional adhesion molecule with disease-specific therapeutic potential.