Recently, the redox function of PDI, in contrast to its chaperone function, was shown to be protective against multiple cellular processes that dysfunction in 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 (Parakh et al., 2020). Here, P4HB is linked to amyotrophic lateral sclerosis.