GSTZ1 (glutathione S-transferase zeta 1) is a bifunctional enzyme with dual roles in cellular detoxification and amino acid metabolism 1. Primarily, GSTZ1 functions as maleylacetoacetate isomerase (MAAI), catalyzing the penultimate step in phenylalanine and tyrosine catabolism 21. The enzyme exhibits glutathione conjugating activity with xenobiotics, including the investigational drug dichloroacetate (DCA), which it metabolizes to glyoxylate, and possesses minimal glutathione peroxidase activity 1. Located primarily in hepatic cytoplasm with lesser mitochondrial localization 1, GSTZ1 participates in broader detoxification of electrophilic compounds and endogenous reactive species formed during oxidative stress 3. Genetically, GSTZ1 exhibits functional polymorphisms with at least four haplotypic variants (1a-1d); haplotype composition influences both enzymatic activity and DCA metabolism rates, with K-carrier variants showing reduced expression in Caucasian populations 45. Physiological chloride and certain anions modulate GSTZ1 inactivation by DCA in haplotype-dependent manner 5. Clinically, GSTZ1 deficiency causes maleylacetoacetate isomerase deficiency (MAAID), a rare condition presenting with elevated succinylacetone at newborn screening 6. However, no definitive clinical disease consequences have been definitively established despite the enzyme's critical metabolic role 1. Additionally, GSTZ1 loss promotes hepatocellular carcinoma metastasis through dysregulated glucuronic acid metabolism and TGFβ pathway activation 7.