Elongator complex protein 1 (ELP1) (ELP1)

Elongator complex protein 1 (ELP1), also known as IKBKAP, is the largest subunit and essential scaffold of the six-subunit Elongator complex (UniProt O95163). Its primary biological function is to facilitate the chemical modification of the wobble uridine (U34) in transfer RNAs (tRNAs), specifically the formation of 5-methoxycarbonylmethyluridine (mcm5U), which is critical for accurate protein translation and proteostasis (PubMed: 29332244, 26261306). While historically associated with transcriptional elongation, its most vital role is now recognized in tRNA-mediated translation regulation and cytoskeleton organization (MedlinePlus). Mutations in the ELP1 gene, particularly a tissue-specific splicing defect, are the primary cause of Familial Dysautonomia (FD), a rare neurodegenerative disorder (PubMed: 29290691). Furthermore, ELP1 has been identified as a major predisposition gene for Sonic Hedgehog-driven medulloblastoma (PubMed: 32350466). Therapeutic strategies include splicing modulators like kinetin and PTC717, as well as gene replacement therapies currently under investigation (Annals of Clinical and Translational Neurology, 2025). Monitoring ELP1 protein levels in the blood and assessing tRNA modification status serve as key biomarkers for evaluating target engagement and therapeutic efficacy (Neurology, 2025).

Other names

IKBKAPIKAPDYSIKI3TOT1p150Inhibitor of kappa light polypeptide gene enhancer in B-cells kinase complex-associated protein

Splicing modulation to correct exon 20 skipping, gene replacement via viral vectors, and stabilization of the Elongator complex.