AUH (AU RNA binding methylglutaconyl-CoA hydratase) is a bifunctional mitochondrial enzyme with dual roles in leucine catabolism and RNA metabolism. Primarily, AUH catalyzes the fifth step of leucine degradation, reversibly converting 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA), which is subsequently cleaved to acetyl-CoA and acetoacetate 123. The enzyme also possesses itaconyl-CoA hydratase activity, detoxifying itaconate—an antimicrobial metabolite produced by macrophages during infection 4. Additionally, AUH functions as an AU-rich element (ARE)-binding protein, targeting mRNA sequences that direct rapid degradation and deadenylation 5. Disease relevance is significant: pathogenic AUH variants cause 3-methylglutaconic aciduria type 1 (MGCA1), an inborn error characterized by decreased enzyme activity, elevated urinary 3-methylglutaconic acid, and variable clinical outcomes ranging from asymptomatic presentation to severe encephalopathy with basal ganglia involvement 6. Recent evidence indicates AUH is a therapeutic target in hepatocellular carcinoma, where post-translational acetylation at K109 inhibits its activity, promoting leucine accumulation and mTOR activation; restoring AUH function suppresses tumor growth 7. These findings underscore AUH's importance in metabolic homeostasis and disease pathogenesis.