Interestingly, the majority of ALS-associated mutations in TARDBP lie within the unstructured C terminal domain and have been shown to increase TDP-43’s intrinsic propensity to aggregate in vitro and in yeast (Johnson et al., 2009; Jiang et al., 2016; Lim et al., 2016). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.