EIF4H is a eukaryotic translation initiation factor that stimulates the RNA helicase activity of eIF4A within the translation initiation complex 1. It enhances RNA binding selectivity by promoting preferential binding to longer RNA sequences (30-33 nucleotides) compared to eIF4A alone (17 nucleotides), despite maintaining the same RNase-resistant footprint 1. EIF4H shares a common binding site with eIF4B on eIF4A, making their interactions mutually exclusive 1. EIF4H has critical roles in multiple viral infections: it is essential for hepatitis E virus replication through direct interaction with viral ORF1 protein and modulation of the replication complex 2, and serves as an early-stage host dependency factor for SARS-CoV-2 3. In neurological disease, EIF4H dysfunction causes growth retardation, reduced brain volume, impaired neuronal development, and defective learning and memory formation in mice, suggesting contribution to Williams-Beuren syndrome 4. EIF4H downregulation reduces toxic dipeptide production from C9orf72 G4C2 repeats in ALS/FTD 5. Clinically, EIF4H overexpression in lung carcinomas promotes transformation and chemotherapy resistance by selectively enhancing translation of growth and survival factor mRNAs 6. KRT14 interaction with eIF4H modulates ACOX2 translation to drive cisplatin resistance in bladder cancer 7. These findings position EIF4H as a therapeutic target across cancer, antiviral, and neurodegenerative contexts.