EIF4G3 is a component of the eIF4F translation initiation complex, which recognizes mRNA caps and recruits mRNA to the ribosome for translation. It functions as a homolog of EIF4G1 and participates in ATP-dependent unwinding of 5'-terminal secondary structures. Beyond its canonical role in translational initiation, EIF4G3 has been implicated in diverse cellular processes including regulation of autophagy and spermatogenesis. EIF4G3 participates in multiple protein-protein interactions relevant to translation and RNA metabolism. It interacts with the m6A reader PRRC2A to regulate translation efficiency of meiotic cell division genes during spermatogenesis 1, and associates with PIWIL1, eIF3f, and HuR within the chr1 body to enhance translation of fatty-acid-metabolism-related mRNAs in spermatids 2. Additionally, EIF4G3 undergoes alternative splicing events that contribute to antiviral responses 3. Clinically, EIF4G3 dysregulation is associated with multiple cancer types. Circular RNA derived from EIF4G3 promotes gastric cancer progression by sponging miR-335 4, and elevated EIF4G3 expression—particularly as part of m7G methylation-related gene signatures—correlates with poor prognosis in sarcoma and primary bone marrow large B-cell lymphoma 5, 6. In renal cell carcinoma, HIF2α suppresses EIF4G3 translation via microexon regulation to promote disease progression 7. Loss-of-function variants in TSCL1, which assembles translation complexes containing EIF4G3, are enriched in patients with non-obstructive azoospermia 2.