CD38

CD38 (Cluster of Differentiation 38), also known as ADP-ribosyl cyclase 1 or cyclic ADP-ribose hydrolase, is a type II transmembrane glycoprotein that functions as a multifunctional ectoenzyme. It catalyzes the synthesis of cyclic ADP-ribose (cADPR) from NAD+, regulating intracellular calcium signaling, and participates in NAD+ metabolism. CD38 also mediates immune cell adhesion and signaling, particularly in lymphocyte activation and apoptosis. Its enzymatic activity intersects with pathways involving calcium mobilization (via ryanodine receptors), sirtuin-mediated metabolic regulation, and immune checkpoints. Overexpression of CD38 is implicated in hematological malignancies (e.g., multiple myeloma, CLL) and autoimmune disorders. Therapeutic anti-CD38 monoclonal antibodies (daratumumab, isatuximab) have revolutionized myeloma treatment by inducing antibody-dependent cellular cytotoxicity and complement-mediated lysis. Emerging therapies targeting CD38 include bispecific antibodies and antibody-drug conjugates in clinical trials for refractory cancers.