CD83 is a transmembrane glycoprotein expressed on activated immune cells including dendritic cells, T cells, B cells, and monocytes that functions as an immune checkpoint regulator rather than a typical co-stimulatory molecule 1. CD83 plays an essential role in CD4+ T cell selection, differentiation, and stability by regulating MARCHF8 activity and preventing ubiquitination-mediated degradation of MHCII and CD86 2. CD83 is a marker of dendritic cell maturation, with membrane-bound CD83 (mCD83) increasing during DC differentiation 3 and interacting with GRASP55 to regulate glycosylation and surface expression 4. Beyond T cell development, CD83 controls and resolves immune responses, maintaining balance between tolerance and inflammation 1. The soluble form (sCD83) exhibits immunosuppressive properties, promoting macrophage alternative activation and reducing pro-inflammatory responses 5. Clinically, CD83 overexpression on CD4+ T cells and B cells correlates with poor outcomes in graft-versus-host disease (GVHD), establishing it as a diagnostic marker 6. CD83-targeted CAR T cells show promise for GVHD prevention and treatment while maintaining anti-leukemia activity 7, warranting investigation as a therapeutic target in transplantation and malignancies 8.