TARDBP and amyotrophic lateral sclerosis: This lends support to the broader concept of ALS as a disorder of RNA metabolism in which a diverse array of RNA binding proteins can be involved, likely in several different mechanisms ranging from mutations resulting in gain- or loss-of-function of RNA binding proteins [including fused in sarcoma (FUS) and TDP-43] to also including those proteins in which ALS-associated mutations confer novel RNA interacting capacity [for instance as observed with mutations in copper/zinc superoxide dismutase (mtSOD1)] (25–27).