NUDT18 (nudix hydrolase 18, also known as MTH3) is a metabolic enzyme with dual substrate specificity. Primarily, it hydrolyzes oxidized nucleoside diphosphates, particularly 8-oxo-dGDP and 8-oxo-GDP with high efficiency, converting them to monophosphates 1. This activity distinguishes NUDT18 from related enzymes MTH1 and MTH2, which preferentially cleave triphosphate forms 2. Recently, NUDT18 was identified as an efficient catalyst for isoprene pyrophosphate hydrolysis, with geranyl pyrophosphate as its best substrate (catalytic efficiency 2.1 × 10⁵ M⁻¹·s⁻¹), suggesting involvement in isoprenoid metabolism and protein isoprenylation regulation 3. NUDT18 also hydrolyzes triphosphate forms of antiviral nucleoside analogs, including remdesivir-TP, ribavirin-TP, and molnupiravir-TP, potentially limiting their therapeutic efficacy 4. Functionally, NUDT18 appears dispensable for oxidative stress resistance in cultured cells, unlike MTH1/MTH2; however, NUDT18 knockout cells show reduced proliferation, indicating roles beyond nucleotide sanitization 5. In disease context, NUDT18 expression is elevated in endometrial cancer relative to normal tissue, and notably, higher expression correlates with favorable prognosis and reduced tumor stage 6. Additionally, dysregulation of NUDT18 was identified in multiple sclerosis with sex-specific differences 7.