NUDT4 is a nudix hydrolase that catalyzes diphosphorylation of inositol polyphosphates and diadenosine polyphosphates, functioning primarily in signal transduction pathways 1. It cleaves beta-phosphates from diphosphoinositol polyphosphates (PP-InsP5, PP-InsP4, [PP]2-InsP4) and diadenosine polyphosphates (Ap6A, Ap5A), with the latter serving as downstream effectors of cardiac KATP channel signaling 1. NUDT4 also hydrolyzes 5-phosphoribose 1-diphosphate to generate ribose 1,5-bisphosphate, a glycolytic activator 2. Beyond its enzymatic functions, NUDT4 plays significant roles in multiple disease contexts. In pancreatic cancer, NUDT4 interacts with circCGNL1 to promote HDAC4 dephosphorylation, triggering HDAC4 nuclear translocation and subsequent RUNX2-mediated GAMT activation for apoptosis induction 3. NUDT4 emerges as a prognostic biomarker in non-small cell lung cancer 4, COVID-19 severity 5, diabetic nephropathy 6, sepsis 7, and heart failure 8, where it associates with immune microenvironment alterations. Genetic variants in NUDT4 show associations with bipolar disorder 9 and menopausal hot flashes 10, suggesting broader neurobiological relevance. These findings position NUDT4 as both a fundamental signaling enzyme and a potential therapeutic target across diverse pathological conditions.