The aggregation of TDP-43 is thought to be driven by a structural change of an α-helical region in the C-terminus that transitions into a cross-β sheet structure.25,26 This structural transition has been shown to be accelerated by disease mutations in the α-helical region,27 although TDP-43 aggregation also occurs in the absence of mutations in most ALS cases. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.