NAD kinase (NADK) is a cytosolic enzyme that catalyzes the phosphorylation of NAD+ to produce NADP+, serving as the sole known pathway for NADP biosynthesis in prokaryotic and eukaryotic cells 1. This reaction generates NADPH, a critical cofactor for reductive biosynthetic pathways and cellular redox homeostasis 2. NADK functions conditionally are determined by metabolic context; it is essential for folate-dependent nucleotide synthesis under low folic acid availability by supporting dihydrofolate reductase activity 2, and is required for cytosolic NADPH-driven ferroptosis regulation 3. NADK activity is regulated through posttranslational modifications, including phosphorylation by NUAK1 at serine 64, which mitigates reactive oxygen species accumulation 4, and through tetramer conformation modulated by N-terminal methylation 5. Disease relevance spans multiple pathologies: in nonalcoholic steatohepatitis, NADK is a primary target of miR-690, with elevated NADK levels contributing to disease progression 6; in non-small cell lung carcinoma, NADK phosphorylation by NUAK1 confers osimertinib resistance by reducing chemotherapy-induced ROS 4, while NADK mutations can increase chemotherapy sensitivity 5; in myocardial ischemia/reperfusion injury, YAP-mediated NADK transcription provides cardioprotection 7; and in Alzheimer's disease, NADK activation ameliorates neuronal ferroptosis 8.