From an overall perspective regarding the pathological effects of proteinopathies, the sALS and fALS categorization may be altered to better consider the underlying mechanisms and cellular consequences as the defining feature, giving thus rise to three key types: ALS-TDP, ALS-SOD1 and ALS-FUS. Furthermore, we propose that future research should also focus on mechanisms underlying proteinopathies in other related tissues that have so far been largely missed, thereby widening the concept of disease to include multisystem proteinopathy. This evidence concerns the gene FUS and amyotrophic lateral sclerosis.