DDX31 is a DEAD-box RNA helicase localized to the nucleolus that plays critical roles in ribosome biogenesis and tumor suppression pathways. DDX31 possesses DNA and RNA-dependent ATPase activity 1 and functions primarily through its interaction with nucleophosmin (NPM1) in the nucleolus 2. In normal cellular context, DDX31-NPM1 complex promotes ribosomal RNA biogenesis; when DDX31 is attenuated, NPM1 translocates to the nucleoplasm and binds HDM2, reducing HDM2-p53 interactions and stabilizing p53, triggering G1 arrest and apoptosis 2. DDX31 is significantly upregulated in renal cell carcinoma (RCC) where it serves as an independent prognostic factor, and its overexpression promotes cell proliferation 2. In bladder cancer, cytoplasmic DDX31 cooperates with mutant p53 and EGFR to promote invasion and EGFR-Akt signaling 3. In head and neck cancer, DDX31 undergoes TRIM25-mediated K63-linked polyubiquitination and degradation; TBC1D14-induced DDX31 degradation suppresses ribosome biogenesis and lymph node metastasis 4. DDX31 also participates in germ cell development pathways and acts as a hub gene in infertility-associated networks 5. These findings establish DDX31 as a multifunctional regulator linking ribosome biogenesis, p53 signaling, and cancer progression.