CD6 is a cell surface adhesion molecule expressed on T cells, NK cells, and thymocytes that mediates multiple immune functions 1. Functionally, CD6 acts as a costimulatory molecule that promotes T-cell activation and proliferation through interactions with its ligands CD166/ALCAM and CD318/CDCP1, while contributing to immunological synapse formation 1. Beyond adaptive immunity, CD6 functions as a calcium-dependent pattern receptor that binds both Gram-positive and Gram-negative bacterial components—lipopolysaccharide (LPS) and lipoteichoic acid—triggering MAP kinase signaling cascades and pro-inflammatory cytokine secretion [UniProt function]. Clinically, CD6 represents a significant therapeutic target due to its involvement in multiple diseases. Genome-wide association studies and Mendelian randomization analyses establish CD6 as a genetic risk factor for inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and stroke 234. Additionally, CD6-ALCAM signaling participates in age-related muscle and bone degeneration 5. The therapeutic potential of CD6 targeting extends to cancer immunotherapy, where blocking CD6-ligand interactions enhances cytotoxic T-cell responses 67. CD6-depleted cell preparations have shown promise in hematopoietic stem-cell transplantation for reducing graft-versus-host disease 8. These diverse functions position CD6 as a multifaceted therapeutic target across autoimmune, inflammatory, oncologic, and transplantation contexts.