Recent studies have established a mechanism by which aberrant RNA splicing caused by mutant TDP-43 or depletion of nuclear TDP-43 contributes to ALS through a loss of function and/or a gain of function (Deshaies et al., 2018; Fratta et al., 2018; Sivakumar et al., 2018). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.