As outlined above, ALS and FTD are marked by mislocalization and aggregation of TDP-43 or FUS – at times in combination with other RBPs – and emerging evidence suggests that these protein pathologies propagate through the nervous system following a prion-like cascade, ultimately causing neurodegeneration via loss-of-function and/or toxic gain-of-function mechanisms. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.