CD38 glycoprotein (cluster of differentiation 38, cyclic ADP ribose hydrolase) (CD38)

CD38 glycoprotein is a type II transmembrane protein first identified as a lymphocyte marker, later found to be broadly expressed in immune and non-immune tissues. It acts both as a receptor and an ectoenzyme, catalyzing the conversion of NAD+ to cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate, which function as secondary messengers in calcium signaling. It also participates in cell adhesion and signal transduction pathways and serves as a metabolic sensor for extracellular NAD+ metabolism. CD38 is highly and uniformly expressed on malignant plasma cells in multiple myeloma and on certain leukemic blasts, making it an attractive target for monoclonal antibodies and CAR-T cell therapies. Drugs targeting CD38 mostly function by direct cytotoxicity or immunomodulation. While these therapies are effective, notable safety concerns include infusion reactions and effects on normal CD38-expressing cells. CD38 is also implicated in age-related decline in NAD+ and chronic inflammation, underscoring its relevance beyond cancer.

Other names

cyclic ADP-ribose hydrolasecluster of differentiation 38ADP-ribosyl cyclase

Antibody-mediated cell killing (antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity); CAR-T cell-mediated cytotoxicity; inhibition of enzymatic activity (blocking NAD+/cADPR pathways); immunomodulation (modulating adenosine production, immune cell activity).