Whiteley and others demonstrated that UBQLN2 facilitates PEG10-ORF1/2 protein degradation and much of it is proteasome-dependent in cells, and the PEG10-ORF1/2 protein is specifically upregulated in the spinal cord of ALS patients compared to healthy controls (Whiteley et al., 2021; Black et al., 2023). Here, UBQLN2 is linked to amyotrophic lateral sclerosis.