ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1

CD38 is a multifunctional transmembrane glycoprotein with ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase enzymatic activities (UniProt: P28907). It synthesizes cyclic ADP-ribose (cADPR) and nicotinate-adenine dinucleotide phosphate (NAADP+), both important second messengers for calcium mobilization and glucose-induced insulin secretion. Beyond its enzymatic roles, CD38 functions as a receptor for CD31, mediating lymphocyte activation and migration across endothelial barriers, and regulates dendritic cell maturation.

CD38 is widely expressed across tissues and immune cells, where it contributes to both metabolic signaling and adaptive immune responses (UniProt: P28907). Its calcium-mobilizing functions and receptor-mediated signaling make it relevant to multiple physiological processes, though no baseline disease associations are listed in UniProt.

CD38 is upregulated in Alzheimer's disease brain tissue. Quantitative proteomics of post-mortem AD brain compared to age-matched controls identified CD38 as significantly elevated with a mean log2 fold-change of 0.6443 (Chaparral AD proteomics). This upregulation was detected across subcellular fractions in TMT-labeled tandem mass spectrometry analysis, suggesting a potential role in AD-associated neuroinflammatory or metabolic dysregulation.