TK2

Thymidine kinase 2 (TK2), encoded by the TK2 gene, is a mitochondrial deoxynucleoside kinase with key roles in nucleotide metabolism. Common aliases include dTk2 and mitochondrial thymidine kinase. It catalyzes phosphorylation of thymidine and deoxycytidine to monophosphate forms, supplying precursors for mitochondrial DNA (mtDNA) synthesis/repair via the salvage pathway—distinct from cytoplasmic de novo nucleotide production.
TK2 biallelic mutations cause mtDNA depletion syndromes (MDS), presenting as infantile/adult myopathy or encephalomyopathy. It intersects with mitochondrial energy metabolism and mtDNA maintenance pathways. Therapeutic efforts focus on nucleotide replacement therapies: deoxynucleoside supplements bypass TK2 dysfunction, with preclinical studies restoring mtDNA levels; some candidates are in early clinical trials for MDS patients.