ANXA2R (annexin A2 receptor) is a protein-binding receptor expressed across multiple tissues with emerging roles in immune regulation and cell survival. While UniProt annotations suggest it may act as a receptor for annexin II to induce osteoclast formation, recent evidence reveals broader functional importance. ANXA2R serves as a novel T cell receptor (TCR)-associated marker, showing strong positive correlations with CD8+ T cell infiltration and T cell-mediated rejection following renal transplantation 1. In melanocyte biology, ANXA2R expression is suppressed through DNA hypermethylation under oxidative stress, leading to increased apoptosis and impaired survival signaling through reduced keratinocyte stem cell factor (SCF) secretion—a key mechanism in vitiligo pathogenesis 2. ANXA2R has been identified as a direct target of miR-139-3p, with downregulation of ANXA2R associated with reduced hepatocellular carcinoma growth and metastasis 3. Additionally, ANXA2R expression correlates with worse overall survival in renal cell carcinoma 4 and mediates cathepsin F effects on breast cancer risk 5. Early ANXA2R T cell markers show strong correlation with Glasgow Coma Scale severity in pediatric traumatic brain injury 6. These findings indicate ANXA2R functions as a multifaceted regulator of immune cell activation, cell survival, and disease progression with potential diagnostic and therapeutic significance across multiple pathologies.