P4HB and amyotrophic lateral sclerosis: However, surprisingly, we found that the redox function of PDI was protective against a broad range of events linked to ALS; protein misfolding, mislocalization of TDP-43 to the cytoplasm, ER stress, inhibition of ER-Golgi transport, and apoptosis; in neuronal cells expressing pathological forms of TDP-43 or SOD1.