EIF4A3 is an ATP-dependent RNA helicase that functions as a core component of the exon junction complex (EJC), a multiprotein assembly deposited at pre-mRNA splice sites 1. During pre-mRNA splicing, EIF4A3 binds spliced mRNAs 20-24 nucleotides upstream of exon-exon junctions in a sequence-independent manner, marking these junctions for downstream processing 12. The EJC remains associated with mature mRNAs throughout metabolism, influencing nuclear export, subcellular localization, translation efficiency, and nonsense-mediated decay (NMD) 13. EIF4A3's ATPase activity is dynamically regulated—induced by CASC3 but inhibited by the MAGOH-RBM8A heterodimer, which stabilizes the ATP-bound EJC on mRNA 1. Beyond canonical splicing, EIF4A3 regulates circular RNA (circRNA) biogenesis and function. It promotes circRNA cyclization and cytoplasmic export by binding back-spliced junction sites 456. EIF4A3 also facilitates cap-independent circRNA translation and participates in EJC-dependent mechanisms that regulate mRNA stability 78. Dysregulation of EIF4A3 associates with cancer chemoresistance, metastasis, and muscle atrophy through circRNA-dependent pathways 456. These pleiotropic functions underscore EIF4A3's central role in gene expression regulation and disease pathogenesis.