In conclusions, we demonstrated that, unlike in SBMA mice, SQSTM1 served as an onset accelerating factor for SOD1-linked toxicities, at least, in a SOD1H46R-expressing ALS mouse model, implying that SQSTM1 upregulation might not always to be beneficial to the treatment of ALS. Here, SQSTM1 is linked to amyotrophic lateral sclerosis.