EIF4G3 is a eukaryotic translation initiation factor and functional homolog of EIF4G1 that serves as a core component of the eIF4F complex 1. As part of eIF4F, EIF4G3 mediates mRNA cap recognition, ATP-dependent unwinding of 5'-terminal secondary structures, and ribosomal recruitment of mRNAs during translational initiation 1. EIF4G3 participates in spermatid development and is involved in regulating translational initiation through its RNA binding activities 23. In spermatogenesis, EIF4G3 assembles into translation-regulatory complexes, including PIWIL1/eIF3f/HuR/eIF4G3 complexes that enhance translation of fatty-acid-metabolism-related mRNAs 3. EIF4G3 also functions in negative regulation of autophagy and interacts with HMGB1 during cellular stress responses 4. Disease relevance includes its upregulation by HIF2α to inhibit MLYCD translation in renal cell carcinoma, promoting lipid accumulation and cancer progression 5. Additionally, EIF4G3 mutations are associated with sarcoma prognosis as part of m7G-methylation-related gene signatures 6, and EIF4G3 mutations appear in primary bone marrow large B-cell lymphoma 7. TSCL1 variants affecting EIF4G3-containing complexes are enriched in male infertility patients with non-obstructive azoospermia 3.