Since FUS, TDP-43, hnRNPA2, TAF15 and EWS each form cytoplasmic aggregates when ectopically expressed in yeast—much like naturally occurring yeast prion proteins—it has been straightforward to monitor how specific ALS-linked mutations alter the proteins’ intrinsic propensity to aggregate and exert toxicity, especially when coupled with in vitro aggregation assays. This evidence concerns the gene FUS and amyotrophic lateral sclerosis.