The finding that autophagy induction suppressed TDP43 toxicity but was harmful in ALS/FTD models involving UBQLN2 and C9ORF72 mutations undermines the notion that autophagy enhancement is a strategy that can be broadly applied to ALS/FTD and related neurodegenerative disorders. The gene discussed is UBQLN2; the disease is amyotrophic lateral sclerosis.