In human ALS muscle, mitochondrial defects including dysregulation of respiratory complex I (44), decreased respiratory complex I and IV activity (45, 75), decreased muscle mitochondrial protein expression (75) and upregulation of muscular mitochondrial uncoupling protein 3 (76) indicate that impairments in mitochondrial function could serve as a metabolic marker of ALS. Here, UCP3 is linked to amyotrophic lateral sclerosis.