DCTD (dCMP deaminase) is a cytoplasmic pyrimidine nucleotide metabolic enzyme that catalyzes the deamination of dCMP to dUMP, providing an essential substrate for thymidylate synthase in dTMP biosynthesis 1. Beyond canonical nucleotide metabolism, DCTD functions in epigenetic nucleotide salvage by catalyzing the first step in a two-step pathway that eliminates 5-hydroxymethyl-dCMP (hmdCMP), an epigenetically modified nucleotide, through deamination to 5-hydroxymethyl-dUMP, which is subsequently hydrolyzed to 5-hydroxymethyluracil 2. Recent investigations have revealed DCTD's role in chemotherapy sensitivity: loss of DCTD confers resistance to the DNA methyltransferase inhibitor decitabine, indicating that 5-aza-dUMP generation contributes to cytotoxicity 3. Additionally, DCTD has been identified as a regulator of ferroptosis in glioblastoma, suggesting therapeutic potential in cancer treatment 4. These findings position DCTD as a critical enzyme at the intersection of nucleotide metabolism, epigenetic regulation, and cancer cell vulnerability, with implications for optimizing nucleoside analogue-based therapies.