NAT10 is an N4-acetylcytidine (ac4C) acetyltransferase that catalyzes acetylation of cytidine residues on mRNAs, 18S rRNA, and tRNAs 1. This RNA modification enhances mRNA stability and translation efficiency, with ac4C preferentially enriched at wobble cytidine sites 1. NAT10 is essential for early ribosomal RNA processing and is a structural component of the small subunit processome 2. Beyond RNA modifications, NAT10 can acetylate protein lysine residues, though the physiological significance remains unclear 1. Mechanistically, NAT10 requires the adapter protein THUMPD1 for tRNA acetylation but not rRNA modification 3. Recent studies reveal ac4C-dependent roles in disease pathogenesis: NAT10 drives cardiac remodeling by stabilizing CD47 and ROCK2 mRNAs 4, promotes osteosarcoma via ATF4/ASNS-mediated asparagine biosynthesis 5, enhances AML through serine metabolism reprogramming 6, and mediates cisplatin chemoresistance in bladder cancer by stabilizing AHNAK mRNA 7. NAT10 also promotes vascular remodeling by acetylating ITGB1 and Col1a2 mRNAs 8. Pharmacological NAT10 inhibitors like Remodelin show therapeutic efficacy in multiple cancer models 4578, positioning NAT10 as an emerging therapeutic target for epitranscriptomic-driven diseases 9.