Eif4h, short for eukaryotic translation initiation factor 4H, is an activator of the RNA helicase eIF4A. It plays a crucial role in the translational control of mRNAs, facilitating the unwinding of secondary structure in the 5'-untranslated region of mRNA, which is essential for ribosome recruitment and protein synthesis [3,4,5]. This process is integral to many biological functions and is associated with pathways related to cell growth, survival, and proliferation.

In lung carcinomas, eIF4H is overexpressed and can predict response to chemotherapy. Depletion of eIF4H in lung cancer cells enhances chemotherapy sensitization, decreases cell migration, and inhibits tumor growth in vivo, with reduced translation of mRNAs encoding cell-proliferation, angiogenic, and anti-apoptotic factors [1]. In a Drosophila model for C9orf72-associated ALS, downregulation of eIF4H reduced toxicity caused by expanded G4C2 and decreased production of toxic GR dipeptides from G4C2 transcripts [2]. In SARS-CoV-2 infection studies, eIF4H was identified as a strong host dependency factor acting early in infection [6]. In lung adenocarcinoma, miR-519d targets eIF4H to inhibit cell proliferation and invasion [7].

In conclusion, Eif4h is essential for translational control and impacts multiple biological processes and disease conditions. Studies using various models, including in vivo models, have revealed its role in cancer, neurodegenerative diseases, and viral infections. These findings provide potential molecular targets for therapies in these disease areas.