The concept of alternative isoforms leading to a change in subcellular localization of ALS-related RBPs is supported by a recent report of a C terminus truncated short TDP-43 (sTDP-43) isoform that introduces a nuclear export signal and exhibits up-regulation and cytosolic aggregation in a hyperexcitability-dependent manner (60). The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.