NUDT14 (nudix hydrolase 14) is a cytosolic nucleotide metabolizing enzyme that primarily hydrolyzes UDP-glucose to glucose 1-phosphate and UMP, with secondary activity on ADP-ribose to ribose 5-phosphate and AMP 1. The enzyme exhibits poor activity on related substrates including ADP-glucose, CDP-glucose, GDP-glucose, and GDP-mannose. NUDT14 functions as a UDP-glucose pyrophosphatase that can be phosphorylated and activated by AMP-activated protein kinase (AMPK), thereby negatively regulating glucosylceramide biosynthesis by depleting intracellular UDP-glucose levels 1. At the cellular level, NUDT14 interacts with human cytomegalovirus RL13 protein, and suppression of NUDT14 expression increases viral DNA replication, suggesting a role in antiviral defense 2. Clinically, NUDT14 has been implicated in multiple disease contexts: a 3'-UTR tandem repeat in NUDT14 is linked to cortical surface area variation in the brain 3, the gene was identified as overexpressed in rectal carcinoma 4, and NUDT14 ranks among eight prognostic genes in uveal melanoma prognosis prediction 5. Additionally, homozygous deletion of NUDT14 contributes to 14q32 deletion syndrome presenting with intellectual disability and facial dysmorphisms 6. NUDT14 emerges as a tractable drug target, with dual NUDT5/14 inhibitors recently developed 7.