THUMPD1 (THUMP domain 1 NAT10 acetyltransferase adaptor) functions as a tRNA-binding adapter protein that mediates NAT10-dependent acetylation of cytidine to N4-acetylcytidine (ac4C) on transfer RNAs 1. Beyond tRNA modification, THUMPD1 facilitates NAT10-catalyzed ac4C modification of primary microRNAs, enhancing their processing into mature miRNAs by promoting DGCR8 interaction 2. Mechanistically, ac4C12 modification on tRNAs improves aminoacylation efficiency and translational fidelity, particularly for Ser/Leu-containing codons 3. Loss of THUMPD1-dependent tRNA acetylation reduces tRNA aminoacylation, causes ribosome stalling, and activates eIF2α phosphorylation stress signaling 4. Additionally, THUMPD1 promotes breast cancer cell invasion and metastasis through AKT-GSK3β-Snail pathway activation, with cytosolic (but not nuclear) expression correlating with advanced cancer stage and poor prognosis 5. Clinically, THUMPD1 mutations cause neurodevelopmental disorders with speech delay and variable ocular anomalies 6. Thumpd1 knockout mice exhibit growth defects and sterility, while concurrent Thumpd1/Gcn2 deletion causes penetrant postnatal lethality, indicating critical roles in mammalian development 4. The gene has been confirmed as causative of intellectual disability in consanguineous populations 7.