Finally, based on the integration of human-Drosophila transcriptomes that identified 16 conserved human neuroprotective transcript changes, we used pharmacological inhibition and genetic manipulation to show that the expression levels of a conserved small conductance Ca2+-activated potassium channel, which is increased in the ALS models, can be manipulated to mitigate the death of human C9ORF72-ALS motor neurons as well as the neurodegeneration-associated locomotor deficits in Drosophila. Here, C9orf72 is linked to amyotrophic lateral sclerosis.