ELP4 (elongator acetyltransferase complex subunit 4) is a core component of the conserved Elongator complex, functioning as part of the accessory Elp456 subcomplex. ELP4 contributes to the Elongator's primary role in catalyzing multiple tRNA modifications, including mcm5U, mcm5s2U, ncm5U, and carboxymethyluridine at the wobble position 34 of tRNAs 1. The Elp456 subcomplex possesses ATP-modulated tRNA binding activity 1, with ELP4 forming a RecA-ATPase-like fold structure critical for ring-shaped assembly and substrate recognition 2. Clinically, ELP4 mutations cause neurodevelopmental disorders through impaired tRNA modification activity. Pathogenic variants in ELP4 are associated with developmental delay, epilepsy, intellectual disability, and motor dysfunction 3. Copy-number deletions of ELP4 are linked to language impairment, autism spectrum disorder, and mental retardation, with significantly elevated prevalence in affected individuals compared to controls 4. ELP4 variants also correlate with intracranial arachnoid cyst severity, affecting inflammatory markers 5. Unlike Elp123 mutations, Elp456 mutations demonstrate distinct neuropathology in animal models, revealing previously unrecognized functional divergence of Elongator subcomplexes during neurodevelopment 3. The functional conservation between human and yeast ELP4 suggests mechanistic insights into both disease pathogenesis and potential therapeutic approaches 6.