DHX15 is a DEAH-box RNA helicase with dual roles in mRNA processing and antiviral immunity. In splicing, DHX15 initiates spliceosome disassembly after mRNA release by detecting ligated mRNA through interaction with disassembly factors TFIP11 and C19L1, which dock and activate DHX15 on catalytic U6 snRNA 1. DHX15 also regulates rRNA and snRNA 2'-O-methylation through interaction with cofactor GPATCH4 2, and its G-patch protein interactions modulate splicing quality control in disease contexts 3. In antiviral innate immunity, DHX15 functions as a viral dsRNA sensor, activating MAVS-dependent interferon signaling 4. In intestinal epithelium, DHX15 cooperates with NLRP6 inflammasome to recognize viral RNA and restrict enteric virus infection through IL-18 maturation 5. DHX15-mediated signaling also coordinates with RNase L-induced apoptosis through interactions with RIG-I and MAVS, promoting caspase-3-dependent cell death independent of interferon transcription 4. Clinically, DHX15 mutations associate with core-binding factor acute myeloid leukemia pathogenesis 6, and genetic variants affecting DHX15 signaling predispose to severe COVID-19 7. Additionally, DHX15 serves as a pathogenic effector target for Fusobacterium nucleatum in KRAS-mutant colorectal cancer, where DHX15 deletion attenuates tumor progression 8.