NMNAT3 (nicotinamide nucleotide adenylyltransferase 3) is a mitochondrial enzyme that catalyzes NAD+ synthesis from nicotinamide mononucleotide (NMN) and ATP, playing a crucial role in cellular NAD+ homeostasis 1. The enzyme exhibits bidirectional activity, also catalyzing the pyrophosphorolytic cleavage of NAD+ to maintain NAD+ pools during periods of excessive consumption 1. NMNAT3 functions as a mitochondrial rheostat, maintaining cellular NAD+ levels through import via SLC25A51 and reversible NAD+ cleavage when present 1. Beyond its enzymatic function, NMNAT3 serves as a stress-response chaperone protein that prevents toxic protein aggregation, independent of its NAD+ synthesis activity. The enzyme is essential for red blood cell function, as NMNAT3 deficiency causes hemolytic anemia through drastically reduced NAD+ levels and altered glycolysis 23. In disease contexts, NMNAT3 protein levels are significantly decreased in Parkinson's disease patients' caudate nucleus, correlating inversely with α-synuclein levels and contributing to neurite pathology 4. Additionally, the FOXO1-NMNAT3 axis dysregulation promotes doxorubicin cardiotoxicity through NAD+ depletion 5. These findings establish NMNAT3 as a critical regulator of cellular energy metabolism and a potential therapeutic target for metabolic and neurodegenerative diseases.