Since the discovery of mislocalized cytoplasmic aggregates of 43 kDa trans-active response DNA-binding protein (TDP-43) as the neuropathological hallmark of nearly all ALS cases (Neumann et al., 2006), focus has fallen on mechanisms related to alterations in the function and behavior of TDP-43, particularly its roles in RNA splicing, the stress response and its propensity for aggregation (Taylor et al., 2016). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.