CD24 is a heavily glycosylated cell surface molecule that functions as a critical regulator of immune tolerance and cell differentiation. Mechanistically, CD24 acts as an innate immune checkpoint through interaction with Siglec receptors (particularly Siglec-10 and Siglec-E), which suppresses inflammatory responses to danger-associated molecular patterns by recruiting inhibitory phosphatases SHP-1 and SHP-2 1. This CD24-Siglec engagement delivers 'don't eat me' signals that shield cells from macrophage-mediated phagocytosis 2. In normal physiology, the CD24-Siglec-E axis protects against metabolic dysfunction and obesity-related inflammation 3, while CD24+CD38+ regulatory B cells promote pro-resolving macrophage differentiation through IL-10 and PD-L1 4. CD24 expression is dysregulated in cancer and autoimmune disease. Residual tumor cells after therapy often express elevated CD24, enabling immune evasion 56. CD24 polymorphisms associate with inflammatory bowel disease susceptibility 7. Aberrant CD24+ decidual stromal cell expansion impairs regulatory T cell induction and correlates with recurrent miscarriage 8. Clinically, CD24 represents a promising immunotherapeutic target. Blocking CD24-Siglec interactions enhances macrophage-mediated tumor clearance when combined with conventional therapies 526, and CD24Fc treatment shows efficacy in metabolic disease 3.