Future studies are required to understand to what extent defects at the level of SUMOylation and/or PIAS4 expression and subcellular localization may contribute to ALS-FTD pathogenesis and progression and to clarify whether similar mechanisms may apply to other RBPs that aggregate in ALS-FTD, such as FUS and hnRNPs [17,46,47]. This evidence concerns the gene FUS and amyotrophic lateral sclerosis.