CD6 is a transmembrane glycoprotein primarily found on the surface of T cells, serving as a co-stimulatory molecule that plays a significant role in T cell activation, proliferation, and differentiation. It binds to its ligands, CD166 (ALCAM) and CD318, which are expressed on various cell types, including antigen-presenting cells, epithelial, and endothelial tissues. The interaction of CD6 with its ligands modulates immune responses and is implicated in the pathogenesis of several autoimmune diseases. CD6 has been identified as a susceptibility locus in multiple sclerosis and Behcet’s disease, and its blockade using monoclonal antibodies, such as itolizumab, has shown clinical benefits in conditions like psoriasis. The therapeutic potential of targeting the CD6 pathway is currently being explored in various immune-mediated diseases, highlighting its importance in modulating T cell functions and maintaining immune homeostasis.