Here, we examined the effect of an ALS/FTD-linked UBQLN2 mutant on the proteasome integrity and found that impaired proteasome assembly occurs prior to neurodegeneration in mutant UBQLN2 transgenic rats and that no proteasome alterations were observed in UBQLN2-depleted rats. This evidence concerns the gene UBQLN2 and amyotrophic lateral sclerosis.