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. The gene discussed is UBQLN2; the disease is frontotemporal dementia.