RNA helicase involved in mRNA processing and antiviral innate immunity (PubMed:26494172, PubMed:34161762). Pre-mRNA processing factor involved in disassembly of spliceosomes after the release of mature mRNA (By similarity). In cooperation with TFIP11 seem to be involved in the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns (By similarity). Plays a key role in antiviral innate immunity by promoting both MAVS-dependent signaling and NLRP6 inflammasome (PubMed:26494172). Acts as an RNA virus sensor: recognizes and binds viral double stranded RNA (dsRNA) and activates the MAVS-dependent signaling to produce interferon-beta and interferon lambda-3 (IFNL3) (By similarity). Involved in intestinal antiviral innate immunity together with NLRP6: recognizes and binds viral dsRNA and promotes activation of the NLRP6 inflammasome in intestinal epithelial cells to restrict infection by enteric viruses (PubMed:26494172, PubMed:34678144, PubMed:34161762). The NLRP6 inflammasome acts by promoting maturation and secretion of IL18 in the extracellular milieu (PubMed:34161762). Also involved in antibacterial innate immunity by promoting Wnt-induced antimicrobial protein expression in Paneth cells (PubMed:33483420). ATP + H2O = ADP + H(+) + phosphate ATPase activity is enhanced upon binding to G-patch domain-containing proteins. G-patch domain-containing proteins act like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity, thereby promoting the ATPase activity. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (By similarity). Identified in the Intron Large spliceosome complex (IL, also named intron lariat spliceosome), a post-mRNA release spliceosomal complex containing the excised intron, U2, U5 and U6 snRNPs, and splicing factors; the association may be transient (By similarity). The IL complex exists in two distinct conformations, one with the DHX15 (ILS2) and one without (ILS1) (By similarity). Interacts with TFIP11 (via G-patch domain); indicative for a recruitment to the IL complex (By similarity). Interacts with SSB/La (By similarity). Interacts with GPATCH2 (via G-patch domain); promoting the RNA helicase activity (By similarity). Interacts with NKRF (via G-patch domain); promoting the RNA helicase activity (By similarity). Interacts with NLRP6 (PubMed:26494172). Ubiquitous. Conditional deletion in intestinal epithelial cells leads to impaired antiviral innate immunity, leading to lethality following infection by an RNA virus (PubMed:34161762). Conditional deletion in intestinal epithelial cells leads to impaired antibacterial immunity, characterized by susceptibility to infection by enteric bacteria C.rodentium (PubMed:33483420). Conditional deletion in Paneth cells leads to reduced expression of alpha-defensins and severe DSS (dextran sodium sulfate)-induced colitis (PubMed:33483420). Belongs to the DEAD box helicase family. DEAH subfamily. DDX15/PRP43 sub-subfamily.