Since the initial description of aFTLD-U as a distinct pathological subtype of FTLD characterized by FUS as the pathological protein almost 15 years ago [75], most progress has been made in the characterization of the pathological aggregates and the comparison with pathology in ALS-FUS, including the change in designation from FTLD-FUS to FTLD-FET and the hypothesis that other mechanisms (potentially upstream of the FET proteins) may induce the protein aggregation in these patients [24, 65, 73]. This evidence concerns the gene FUS and amyotrophic lateral sclerosis.