DNPH1 (2'-deoxynucleoside 5'-phosphate N-hydrolase 1) functions as a nucleotide pool sanitizer that eliminates cytotoxic modified nucleotides through hydrolytic cleavage. The enzyme catalyzes the hydrolysis of the N-glycosidic bond in 5-hydroxymethyl-dUMP (hmdUMP), converting this cytotoxic nucleotide into 5-hydroxymethyluracil and 2-deoxy-D-ribose 5-phosphate to prevent genomic integration 1. DNPH1 operates through a two-step mechanism involving formation of a covalent glycosyl-enzyme intermediate, facilitated by a conserved catalytic triad 2. The enzyme exhibits broader substrate specificity, accepting other 2'-deoxynucleoside 5'-monophosphates as slow-reacting substrates 3. DNPH1 activity is naturally regulated by purine nucleotides (ATP, GTP), which act as inhibitors under physiological conditions where their concentrations exceed substrate levels 4. Clinically, DNPH1 represents a promising therapeutic target, as its inhibition sensitizes BRCA-deficient cancer cells to PARP inhibitors by allowing accumulation of genomic hmdU, leading to DNA damage and apoptosis 1. The enzyme has been implicated in treatment resistance mechanisms in various cancers and identified as a potential biomarker for breast cancer risk 56.