TDP-43 proteinopathy is characterized by the abnormal redistribution of TDP-43 from the nucleus into the cytoplasm, leading to both loss and toxic gain-of-function phenotypes: loss of nuclear TDP-43 causes mis-splicing events and cryptic exon inclusion in key neuronal genes such as STMN2 and UNC13A [184–187], whereas accumulated cytoplasmic TDP-43 forms detergent-insoluble aggregates that sequester proteins involved in various cellular pathways [10, 188–191]. This evidence concerns the gene TARDBP and proteostasis deficiencies.