Despite this almost ubiquitous presence of TDP-43 aggregates, TDP-43-centric sALS studies may be considered limited in the scope of a mechanistic understanding of ALS as biochemical alterations and correlations instead reflect a “multiRBP proteinopathy” [1,14], or perhaps to better generalize, a network, multi-proteinopathy that is rooted in RNA dysfunction. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.