CD244 (2B4) is a dual-function immune receptor in the SLAM family that binds CD48 and regulates both innate and adaptive immunity. The receptor exhibits context-dependent activating or inhibitory functions based on adapter protein availability, particularly SAP (SH2D1A) 1. When SAP is present, CD244 activates NK cells and promotes cytotoxicity and IFN-γ production, while SAP absence leads to inhibitory signaling through phosphatases like SHP-1 and SHIP 2. CD244 is expressed on NK cells, T cells, monocytes, dendritic cells, and other immune cells, serving as a systems-level integrator of immune homeostasis 1. In cancer, CD244 has complex roles: it can promote T cell exhaustion when upregulated by TOX in tumor-infiltrating lymphocytes 3, but CD244-deficient macrophages show enhanced anti-tumor activity and improved antigen presentation 4. CD244 expression is altered in autoimmune diseases like systemic lupus erythematosus and serves as a potential therapeutic target in multiple myeloma 5. The receptor also distinguishes circulating NK-like iNKT cell subsets that mediate antitumor immunity 6. These diverse functions make CD244 a promising target for precision immunotherapy across infections, cancer, and autoimmune conditions 7.