NMNAT2 (nicotinamide nucleotide adenylyltransferase 2) is a cytosolic and Golgi-localized NAD+ synthesizing enzyme with dual roles in neuronal maintenance and cancer metabolism. Structurally, NMNAT2 catalyzes the formation of NAD+ from nicotinamide mononucleotide (NMN) and ATP 12, and can perform the reverse pyrophosphorolytic reaction 12. Beyond catalytic function, NMNAT2 acts as an axon maintenance factor that delays Wallerian degeneration, an evolutionarily conserved axonal self-destruction process 3. This neuroprotective function operates through the NMNAT2-NAD+-SARM1 axis: NMNAT2 depletion reduces NAD+ levels, elevating the NMN/NAD+ ratio, which activates SARM1 (a NAD+ sensor) to trigger axonal demise 43. Decreased NMNAT2 expression correlates with neurodegenerative diseases including ALS, Alzheimer's disease, and peripheral neuropathy 3. Additionally, NMNAT2 supports mono-ADP-ribosylation of ribosomal proteins via PARP16, regulating translation and protein homeostasis in ovarian cancer cells 5. NMNAT2 mRNA abundance positively correlates with cognitive capabilities in aging humans 6. Pharmacological NMNAT2 activation via small molecules driving NAD production shows neuroprotective potential 7, representing a promising therapeutic target for neurodegenerative diseases.