In his accounts“On longevity and shortness of life”,Aristotle considered how diseased states could be interchangeably associated with long and short lifespans.He believed that the presence of opposite elements and the environment were the sole determinants of this variability.Nowadays,also struck by the same phenomenon observed by the Greek philosopher,human geneticists are still trying to define the etiological basis of the phenotypic plasticity in neurodegenerative disorders.Among such diseases,amyotrophic lateral sclerosis(ALS)stands out as a highly heterogeneous condition.