Nicotinamide adenine dinucleotide phosphate phosphatase (NADP+ phosphatase) (NADPase)

Nicotinamide adenine dinucleotide phosphate phosphatase (NADP+ phosphatase), notably represented in humans by the circadian-regulated protein Nocturnin (NOCT), is an enzyme that catalyzes the removal of the 2'-phosphate group from NADP+ and NADPH to generate NAD+ and NADH. This enzymatic activity serves as a critical junction in cellular metabolism, governing the balance between the NAD+ pool (used primarily in catabolism and signaling) and the NADP(H) pool (essential for reductive biosynthesis and antioxidant defense). By regulating these nucleotide levels, NADP+ phosphatase influences a wide array of physiological processes, including lipid absorption, adipogenesis, and the response to oxidative stress. In disease contexts, the overactivity or dysregulation of this target is linked to metabolic syndrome, obesity, and hepatic steatosis, where its inhibition has been shown in animal models to provide protection against weight gain and fatty liver disease. Consequently, it has emerged as a novel therapeutic target for metabolic disorders and aging-related conditions, with ongoing research focused on developing specific small-molecule inhibitors to modulate nutrient utilization and enhance cellular resilience.

Other names

NocturninCCRN4LNADPH 2'-phosphohydrolaseNADP+ 2'-phosphohydrolase2'-phosphoadenosine 5'-diphosphoribose phosphataseC1orf123

Inhibition of NADP+ phosphatase (Nocturnin) prevents the dephosphorylation of NADP+ to NAD+, thereby modulating the cellular pools of pyridine nucleotides and altering metabolic processes such as lipid trafficking and storage.