[NAD kinases (NADKs) family proteins: Advances in metabolic regulation mechanisms and disease associations].

Nicotinamide adenine dinucleotide [NAD(H), consisting of its oxidized form NAD+ and reduced form NADH] and nicotinamide adenine dinucleotide phosphate [NADP(H), consisting of its oxidized form NADP⁺ and reduced form NADPH] are core molecular pair governing metabolic regulation, which exert central functions in modulating cellular energy metabolism, redox homeostasis and biosynthesis. The imbalance of intracellular ratio of NAD(H) to NADP(H) can lead to serious pathophysiological consequences and trigger a wide spectrum of diseases. NAD kinases (NADKs), the sole enzymes that phosphorylate NAD(H) to NADP(H), therefore sit at the hub of NAD(H)/NADP(H) balance control. Because NADP+ cannot cross subcellular membranes, eukaryotic NADKs are classified into two isoforms: cytosolic NADK1 and mitochondrial NADK2. The catalytic activity of NADKs is regulated at the transcriptional and post-translational modification levels, and aberrant expression or dysfunction of NADKs is closely linked to the initiation and progression of numerous diseases. Targeted intervention strategies against NADKs thus represent a promising therapeutic avenue for the clinical treatments of tumors, metabolic disorders, and other related diseases.