ENOSF1 (enolase superfamily member 1) is a metabolic enzyme that catalyzes the dehydration of L-fuconate to 2-keto-3-deoxy-L-fuconate, a critical step in L-fucose catabolism. This reaction involves abstraction of the 2-proton to generate an enediolate intermediate stabilized by magnesium ions. The enzyme participates in carbohydrate metabolism and is localized to mitochondria 1. Beyond its primary metabolic function, ENOSF1 has emerged as a pharmacogenomic biomarker. A common intronic polymorphism (rs2612091) is consistently associated with 5-fluorouracil (5-FU) and capecitabine toxicity, particularly hand-foot syndrome, with toxicity-associated alleles conferring independent risk effects 2. This ENOSF1 variant explains previously attributed associations with thymidylate synthase (TYMS) polymorphisms and correlates with ENOSF1 mRNA expression levels rather than TYMS expression 3. The rs2612091-T allele predicts favorable disease-free survival in colorectal cancer patients receiving capecitabine-based adjuvant therapy 4, and similar associations exist in gastric cancer treated with 5-FU 5. Additionally, ENOSF1 peptide regions have been identified as potential serum biomarkers for gastric cancer detection 6. While ENOSF1 mutations are associated with digenic dyskeratosis congenita, its primary clinical relevance currently centers on predicting chemotherapy toxicity and treatment response.