NAT8L (N-acetyltransferase 8 like) is a mitochondrial enzyme that catalyzes N-acetylaspartate (NAA) synthesis from L-aspartate and acetyl-CoA 123. Beyond its canonical metabolic role, NAT8L has emerged as a multifunctional protein with significant disease implications. In cancer biology, NAT8L and NAA levels are elevated in resistant tumors and associated with worse overall survival across multiple cancer types 4. NAT8L suppresses anti-tumor immunity by impairing cytotoxic T cell and NK cell function through NAA-mediated disruption of immunological synapse formation 5. In hepatocellular carcinoma, NAT8L downregulation paradoxically promotes proliferation by increasing cytosolic aspartate availability for purine biosynthesis and the pentose phosphate pathway 6. In neurological contexts, NAT8L protects against Alzheimer's disease pathology by modulating mitochondrial function and reducing amyloid-β toxicity 7. However, NAT8L mRNA oxidation in multiple sclerosis neurons impairs translation, reducing NAA levels and compromising myelin integrity 8. NAT8L also functions in brown adipose tissue, where it regulates lipid turnover and energy expenditure through PPARα-dependent mechanisms 9. These findings position NAT8L as a potential therapeutic target in cancer immunotherapy and neurodegenerative diseases, though its tissue-specific functions require careful consideration.