The dCK/dGK family of proteins includes 4 different deoxyribonucleoside kinases including the cytoplasmic (TK1) and mitochondrial (TK2) thymidine kinases, and the deoxycytidine (dCK) and deoxyguanosine (dGK) kinases. Deoxyribonucleoside kinases catalyze the 5'-phosphorylation of 2'-deoxyribonucleosides with nucleoside triphosphates (NTPs) as phosphate donors. The dCK enzyme is associated with drug resistance and sensitivity, as both dCK and TK2 phosphorylate several antiviral and chemotherapeutic nucleoside analogs. Deficiency of dCK activity corresponds with resistance to antiviral and chemotherapeutic agents. dCK and TK1 localize to the cytosol, whereas dCK and TK2 localize to the mitochondria. These deoxyribonucleoside kinases are most abundantly expressed in muscle, brain and liver.