DHX16 (DEAH-box helicase 16) is an essential RNA helicase that functions in two critical cellular processes: pre-mRNA splicing and innate antiviral immunity. As a core spliceosomal component, DHX16 is required for pre-mRNA splicing after spliceosome formation but prior to the first transesterification reaction 12. The protein catalyzes ATP-dependent remodeling during the transition from activated Bact to branching-competent B* spliceosomes, translocating along introns while stripping away the RES complex and opening the SF3B1 clamp 3. DHX16 also serves as a pattern recognition receptor in antiviral immunity, recognizing specific viral RNA signals that undergo splicing and partnering with RIG-I to amplify innate immune responses through unanchored K48-polyubiquitin chains synthesized by TRIM6 4. Pathogenic variants in DHX16 cause neuromuscular oculoauditory syndrome, characterized by neuromuscular disease, sensorineural hearing loss, retinal abnormalities, and developmental delays 567. Functional studies demonstrate that DHX16 mutations lead to nuclear retention of unspliced pre-mRNAs and impaired spliceosome function 2. The expanding phenotypic spectrum includes mitochondrial deficiency and primary ovarian insufficiency, highlighting DHX16's broader cellular importance 7.