Dominant mutations in the Cu/Zn superoxide dismutase (SOD 1) gene lead to a familial form of amyotrophic lateral sclerosis (ALS), an adult motor neuron disease.Although ubiquitous expression of mutant SOD1 provokes progressive, selective motor neuron degeneration in human and rodents due to an acquired toxic property(ies) of the mutant, the distinct roles of mutant toxicity within motor neurons and non-neuronal cells are recently established by our cell-type specific gene ablation from mutant SOD1 mice.The toxicity(ies) within astrocytes and microglia accelerates disease progression, indicating that glial cells contribute to non-cell autonomous neurodegeneration.