DCK encodes deoxycytidine kinase, a rate-limiting enzyme essential for nucleotide metabolism and anticancer drug activation. The enzyme phosphorylates natural deoxyribonucleosides including deoxycytidine, deoxyguanosine, and deoxyadenosine, displaying broad substrate specificity without chirality selectivity 1. Critically, DCK serves as the rate-limiting enzyme for activating numerous nucleoside analog prodrugs used in cancer and antiviral chemotherapy, including gemcitabine, cytarabine, and cladribine 123. The enzyme's crystal structure reveals key substrate specificity determinants, particularly the interaction between Arg128 and the 2'-arabinosyl position of therapeutic nucleosides 1. Clinically, DCK expression levels correlate with treatment outcomes in multiple malignancies. Higher DCK protein expression associates with improved overall survival and disease-free survival in pancreatic cancer patients receiving gemcitabine therapy 4. Similarly, in meningiomas, elevated DCK expression correlates with enhanced gemcitabine sensitivity and tumor proliferative activity 5. Genetic polymorphisms in DCK, particularly the A9846G variant, significantly influence patient prognosis and drug response 46. Alternative splicing can produce truncated DCK variants (dCK-∆ex2-3) that may contribute to drug resistance in hematological malignancies 7.