TYMS encodes thymidylate synthase, a critical enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) using 5,10-methylenetetrahydrofolate as a cofactor, providing essential nucleotides for DNA synthesis and repair 1 2. The enzyme plays a fundamental role in both nuclear and mitochondrial de novo thymidylate biosynthesis pathways. Recent research demonstrates that TYMS-mediated thymidine nucleotide metabolism critically controls human telomere length, with TYMS knockout decreasing telomere length while thymidine supplementation promotes telomerase-mediated telomere elongation 1. TYMS serves as an important target for chemotherapy agents including 5-fluorouracil and methotrexate, with overexpression linked to drug resistance 2 3. Polymorphisms in the TYMS gene, particularly in the 5' and 3' untranslated regions, influence enzyme expression levels and have been associated with variable responses to chemotherapy and disease susceptibility 2 4. The gene shows clinical relevance across multiple conditions, including potential roles as a biomarker in acute respiratory distress syndrome 5 and associations with breast cancer risk 4, highlighting its broader significance beyond nucleotide metabolism.