CD48 is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that functions as a critical immunoregulatory receptor on hematopoietic cells 1. The protein mediates immune cell activation and adhesion through high-affinity binding to CD244 (2B4) and lower-affinity interactions with CD2 21. Despite lacking an intracellular domain, CD48 stimulation induces lipid raft rearrangement, Lck kinase activity, and tyrosine phosphorylation 1. CD48 plays diverse roles across immune cell types: it facilitates T-cell activation, regulates NK cell cytotoxicity, and mediates eosinophil responses to bacterial pathogens like Staphylococcus aureus 34. In disease contexts, CD48 contributes to multiple myeloma drug resistance when downregulated by KDM6A loss, affecting Daratumumab-mediated antibody-dependent cellular cytotoxicity 5. Additionally, CD48 serves as a novel receptor for GDF15 on regulatory T cells, promoting immunosuppression in hepatocellular carcinoma 6. The receptor is also expressed on immune-specialized megakaryocyte subsets, suggesting additional roles in innate immunity 7. These findings establish CD48 as a versatile immunomodulatory molecule with therapeutic potential in cancer, autoimmunity, and inflammatory diseases 4.