Moreover, analysis of post-mortem α-motor neurons (MNs) of ALS-FTD patients showed an inverse correlation between PIAS4 immunoreactivity and the presence of TDP-43 pathological aggregates, further suggesting that a dysregulation of PIAS4-mediated SUMO2/3-ylation of TDP-43 may contribute to protein aggregation during the course of disease. Here, PIAS4 is linked to amyotrophic lateral sclerosis.