Although some PDIs (i.e., PDIA1) are expressed at high levels in normal cells, to maintain the proper protein folding and/or in response to UPR signaling, several studies have highlighted that PDIA1 and PDIA3 expression is upregulated in various cancers and neurodegenerative diseases [16,17,18,19,20]. This evidence concerns the gene P4HB and neurodegenerative disease.