UXS1 (UDP-glucuronate decarboxylase 1) catalyzes the NAD-dependent conversion of UDP-glucuronic acid to UDP-xylose, a critical step in glycosaminoglycan biosynthesis 1234. The enzyme performs a two-step reaction: oxidation of UDP-glucuronic acid using NAD+ produces an intermediate and NADH, which is then reversed to regenerate NAD+ and form UDP-xylose 14. UXS1 localizes to the Golgi apparatus where it prevents pathological accumulation of UDP-glucuronic acid, which disrupts Golgi morphology and impairs trafficking of surface receptors 5. UXS1 is a conditional metabolic vulnerability in cancers with elevated UGDH expression, including lung adenocarcinoma and KEAP1-mutant lung cancer, where it functions as a detoxification enzyme 56. In KEAP1-mutant tumors, UXS1 loss causes pyrimidine nucleotide depletion and DNA replication stress, inducing cell-cycle arrest or apoptosis 6. The enzyme also represents a selective dependency in certain biliary tract cancers 7. Genetic variants in the UXS1 promoter have been associated with gastroesophageal cancer susceptibility, and inhibition of UXS1 expression reduced cancer cell viability 8. These findings position UXS1 inhibitors as potential therapeutics for KEAP1-mutant and UGDH-overexpressing tumors.