DHX33 (DEAH-box helicase 33) is a multifunctional RNA/DNA helicase that plays critical roles in ribosome biogenesis, immune signaling, and cancer progression. The protein demonstrates dual DNA/RNA unwinding activity coupled with ATPase function 1. In nucleolar organization, DHX33 stimulates RNA polymerase I transcription and associates with ribosomal DNA loci for ribosome biogenesis, while in the cytoplasm it promotes 80S ribosome assembly during translation initiation 23. DHX33 serves as a cytosolic dsRNA sensor, mediating NLRP3 inflammasome formation in macrophages and type I interferon production in dendritic cells through MAPK and NF-κB pathway activation 45. In cancer contexts, DHX33 is frequently overexpressed and promotes tumorigenesis through multiple mechanisms: it acts as a transcriptional coactivator with AP-2β to regulate Bcl-2 expression and prevent apoptosis 6, regulates mevalonate pathway genes downstream of mutant p53 and Ras 7, and controls HMGB family gene transcription through promoter demethylation 89. DHX33 protein stability is regulated by GSK-3β-mediated phosphorylation leading to ubiquitin-mediated degradation, which is disrupted in cancer cells resulting in DHX33 overexpression 10. Clinical significance includes its potential as a prognostic biomarker and therapeutic target in various cancers, particularly lung adenocarcinoma 11.