ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase

ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase is a bifunctional enzyme responsible for both synthesizing and hydrolyzing cyclic ADP-ribose (cADPR), a key intracellular calcium-mobilizing second messenger, from NAD^+^ as substrate[2][4][5]. Human homologs include CD38 (isoform 1) and CD157/BST1 (isoform 2), both of which catalyze the formation of cADPR and also generate other metabolites such as nicotinate adenine dinucleotide phosphate (NAADP), another potent Ca^2+^ mobilizer[4][6]. The enzyme is a member of the glycosylase/hydrolase family (EC 3.2.2.6) and regulates a broad range of biological processes including cell signaling, proliferation, immune responses, and hormone secretion[1][4][9]. CD38, the most clinically relevant isoform, is broadly expressed on hematopoietic and other cell types and is targeted therapeutically in conditions like multiple myeloma. Therapeutic antibodies against CD38 inhibit its enzymatic activity and eliminate CD38-expressing malignant cells, with safety concerns primarily related to immune function[7]. The enzyme's products and activity also have potential biomarker and drug target utility in metabolic and neurodegenerative diseases[5][9].

Other names

ADP-ribosyl cyclaseCyclic ADP-ribose hydrolaseNAD(P) nucleosidaseNicotinamide adenine dinucleotide (phosphate) nucleosidaseTriphosphopyridine nucleotidaseADPRCCD38 (for human isoform 1, gene name)BST1 (for human isoform 2, gene name/CD157)

Antibody-mediated inhibition of CD38 enzymatic activity and cell depletion (e.g., by daratumumab, isatuximab); Inhibition of cADPR/NAADP synthesis, reducing Ca^2+^ signaling and downstream cell functions