Although polyubiquitylation on ALS-related Sod1 mutants has been reported (Urushitani et al., 2002), it is not clear whether the polyubiquitylation or other features, which would be embedded in its primary sequence or its folded conformation, function as a signal to the Cdc48-20S proteasome. Here, VCP is linked to amyotrophic lateral sclerosis.