TARDBP and amyotrophic lateral sclerosis: Taken together, these modifiers of TDP-43 identified through genetic screens in several C. elegans models of ALS represent a group of compelling therapeutic targets and implicate the activity or disruption of ER-associated protein homeostasis, RNA metabolism, protease activity, the innate immune response, proteasomal and autophagic degradation, and other biological pathways in ALS pathogenesis.