UBQLN2 is mutated in familial cases of the protein folding disorder amyotrophic lateral sclerosis (ALS) (Deng et al., 2011), and intriguingly, all familial mutations cluster to the PXXP motif, which is unique to UBQLN2 and of unknown function (Deng et al., 2011, Fahed et al., 2014, Williams et al., 2012, Vengoechea et al., 2013) (Figure 1A). The gene discussed is UBQLN2; the disease is proteostasis deficiencies.