ELP2 encodes a critical component of the Elongator complex, a highly conserved multiprotein assembly essential for tRNA modifications and cellular functions 1. The protein forms part of the catalytic Elp123 subcomplex and is structurally characterized by two seven-bladed WD40 Ξ² propellers that are necessary for binding to Elp1 and Elp3 subunits 2. ELP2 serves as a hub for Elongator complex assembly and functional regulation, with its WD40 fold integrity being essential for complex formation across multiple species 2. The Elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs, including modifications like mcm5U, mcm5s2U, and ncm5U 1. ELP2 mutations cause significant neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, spastic paraplegias, and developmental epileptic encephalopathies 345. These mutations disrupt tRNA modification activity, leading to perturbed protein homeostasis, impaired neurogenesis, myelin loss, and neurodegeneration 3. The protein also binds microtubules through conserved alkaline residues and affects histone H3 acetylation activity 2. Recent studies have expanded the phenotypic spectrum associated with ELP2 mutations to include cortico-cerebellar atrophy, nodular heterotopia, and epilepsy 6.