Very recently, we and others found that Sirt2-/- mice display an alteration of mitochondrial content and morphology, which results in energy failure and redox dyshomeostasis in the CNS [2,3].The axonal degeneration accompanied by redox/mitochondrial dysfunction in aged Sirt2-/- mice [2], is also found in most of the age-related neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), or Amyotrophic Lateral Sclerosis (ALS), as well in common and rare diseases of myelin [4] and in physiological aging. The gene discussed is SIRT2; the disease is amyotrophic lateral sclerosis.