Surprisingly, UBQLN2 knockout models in mice or rats only induced mild age-dependent motor defects [219], while either increased expression of WT UBQLN2 protein or transgenic expression of ALS/FTD mutant UBQLN2 resulted in varying levels of neurodegeneration and motor defects together with the accumulation of ubiquitinated aggregates positive for p62, LC3, TDP-43 and UBQLN2 itself [215,217,220-223]. Here, SQSTM1 is linked to amyotrophic lateral sclerosis.