DHX29 is an ATP-dependent RNA helicase with dual roles in translation initiation and innate immunity. In translation, DHX29 is a core component of the 43S pre-initiation complex that facilitates ribosomal scanning on structured 5'-UTRs by promoting 48S complex formation 1. It binds near the mRNA entrance of the 40S ribosome and cooperates with eIF3 to navigate secondary structures without processive helicase activity 1. Recent evidence reveals DHX29 monitors codon optimality through direct interaction with the 80S ribosome's A-site entrance, recruiting the GIGYF2•4EHP complex to suppress nonoptimal mRNAs 2. Beyond translation, DHX29 functions as a cytosolic nucleic acid cosensor in innate immunity. It directly binds nucleic acids and cooperates with RIG-I and MAVS to trigger type I interferon responses against viral infection 3, and specifically enhances MDA5-mediated antiviral immunity against picornaviruses like EMCV 4. DHX29 depletion impairs cancer cell proliferation both in vitro and in xenografts, suggesting therapeutic potential 5. Gene expression analysis indicates DHX29 may serve as a biomarker for tuberculosis and osteoporosis 67, while CRISPR screening identified DHX29 as a negative regulator of canonical Wnt signaling 8. These findings establish DHX29 as a multifunctional protein integrating translation control with immune surveillance.