Mutations in VCP (8,9), SQSTM1 (10–12), UBQLN2 (13), OPTN (14,15), TBK1 (16,17), DNAJC7 (18) and CYLD (19) have all been associated with ALS/FTD, and all encode components of the ubiquitin-proteasome system (UPS) or autophagic machinery, implicating defective protein degradation in ALS and FTD. This evidence concerns the gene UBQLN2 and amyotrophic lateral sclerosis.