HIBCH (3-hydroxyisobutyryl-CoA hydrolase) is a mitochondrial matrix enzyme that catalyzes the hydrolysis of 3-hydroxyisobutyryl-CoA and isobutyryl-CoA, functioning in valine catabolism and branched-chain amino acid metabolism. The enzyme converts valine metabolites during normal energy production; its activity is essential for proper mitochondrial bioenergetics 1. HIBCH deficiency causes a rare autosomal recessive neurodegenerative disorder characterized by movement disorders, including ataxia and dystonia, with basal ganglia involvement 1. Pathogenically, HIBCH loss leads to abnormal mitochondrial morphology, respiratory chain defects, and elevated lysine methacrylation of mitochondrial proteins, which contributes to disease pathology 2. Ectopic lysine methacrylation-induced protein modification appears mechanistic in HIBCH-deficiency phenotypes, and reducing methacrylation levels partially rescues defects in patient fibroblasts 2. Clinically, HIBCH mutations represent a potentially treatable neurodevelopmental disorder identifiable through exome sequencing in consanguineous families 3. Beyond neurodegeneration, HIBCH dysregulation associates with metabolic disease: elevated plasma 3-HIB (HIBCH product) correlates with fatty liver and insulin resistance 4, while genetic evidence indicates HIBCH inversely associates with type 2 diabetes risk 5. These findings establish HIBCH as relevant to both neurodegenerative and metabolic disease pathways.