NAT10 is an N-acetyltransferase that catalyzes N4-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA, and tRNAs. In mRNAs, ac4C modification enhances stability and translation efficiency, with particular enrichment at wobble cytidine sites 1. NAT10 is essential for early ribosomal RNA synthesis, mediating ac4C formation at specific 18S rRNA positions and participating in the small subunit processome during ribosome biogenesis. Beyond RNA modification, NAT10 can acetylate proteins including histones and p53, though the in vivo significance of this protein acetyltransferase activity remains unclear. NAT10 dysfunction is implicated in multiple cancers. In triple-negative breast cancer, the NAT10-ac4C-JunB-LDHA axis promotes glycolysis and immunosuppression; remodelin, a NAT10 inhibitor, enhanced anti-tumor immune responses when combined with anti-CTLA-4 antibodies 2. In colorectal cancer, NAT10 stabilizes KIF23 mRNA via ac4C modification to activate Wnt/β-catenin signaling, and remodelin showed inhibitory effects in vitro and in vivo 3. Similar ac4C-dependent mechanisms promote progression in cervical cancer via FOXP1, hepatocellular carcinoma via HMGB2, osteosarcoma via ATF4/ASNS, and acute myeloid leukemia via serine metabolism 4567. Remodelin and panobinostat demonstrate pharmacological tractability; paliperidone and AG-401 show promise in osteosarcoma models. Beyond cancer, NAT10 inhibition by remodelin corrected nuclear architecture defects in laminopathies 8, and elevated NAT10 and ac4C levels contribute to cardiac remodeling in heart failure 9.