P4HB and amyotrophic lateral sclerosis: Consistent with this concept, the identification of mutations in UBQLN2/Ubiquilin2 [49], p62/SQSTM1 [50], and PDI [51] in ALS cases points out for a critical role of alterations in the proteostasis network in the disease, where the disruption of detoxification mechanisms emerges as a relevant factor for its initiation and evolution.