NMNAT1 (nicotinamide nucleotide adenylyltransferase 1) catalyzes NAD+ synthesis from nicotinamide mononucleotide (NMN) and ATP, functioning as a key enzyme in the NAD+ salvage pathway 1. The enzyme also catalyzes the reverse pyrophosphorolytic cleavage of NAD+ and can utilize alternative substrates including nicotinic acid mononucleotide and triazofurin monophosphate 1. Mechanistically, NMNAT1 resides primarily in the nucleus, where it governs nuclear NAD+ homeostasis and participates in nuclear ATP generation required for energy-consuming chr1 remodeling events 23. NMNAT1 activity also facilitates PARP1-mediated protein ADP-ribosylation of histones 4. Clinically, NMNAT1 mutations cause Leber congenital amaurosis (LCA), a severe early-onset retinal dystrophy presenting before age one with progressive vision loss 56. The disease phenotype shows gradual progression over decades 5. Gene augmentation therapy using adeno-associated virus delivery of normal NMNAT1 rescued retinal structure and function in mouse models 7. Beyond retinal disease, NMNAT1 dysfunction contributes to alcohol-associated liver disease through impaired hepatic NAD+ homeostasis and lipid metabolism 3. NMNAT1 expression is also therapeutically relevant in glioblastoma, where it activates the prodrug gliocidin into its tumoricidal form 8.