AUH encodes 3-methylglutaconyl-CoA hydratase, a mitochondrial enzyme that catalyzes the fifth step of leucine catabolism, converting 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA, which is subsequently degraded to acetyl-CoA and acetoacetate. The enzyme also possesses itaconyl-CoA hydratase activity, enabling detoxification of itaconate, an antimicrobial metabolite produced by macrophages during infection. Beyond its metabolic roles, AUH binds AU-rich elements in mRNA 3' untranslated regions, potentially regulating mRNA stability and degradation. Pathogenic variants in AUH cause 3-methylglutaconic aciduria type 1 (MGCA1), an inborn error of leucine degradation characterized by accumulation of 3-methylglutaconic acid and related metabolites. Clinical presentations range from asymptomatic to severe encephalopathy with basal ganglia involvement, often detected through elevated acylcarnitine species on newborn screening 12. Diagnosis is confirmed by demonstrating markedly decreased 3-methylglutaconyl-CoA hydratase activity and identifying pathogenic AUH variants 1. Management includes levocarnitine supplementation and dietary protein restriction 1. Recent evidence suggests AUH dysfunction may contribute to tumorigenesis: DLAT-mediated acetylation of AUH at lysine 109 inhibits its activity, promoting leucine accumulation and mTOR activation in hepatocellular carcinoma 3. Restoring AUH function via AUHK109R-mRNA lipid nanoparticles effectively inhibits tumor growth in vivo, indicating therapeutic potential 3.