P4HB and amyotrophic lateral sclerosis: However, PDI is aberrantly modified by S-nitrosylation in ALS patients26 which results in loss of its functional activity24,26 Interestingly, however, PDI colocalizes with FUS in human tissues from both sALS and fALS patients and in cells expressing mutant FUS20, implying that it may be protective against mutant FUS given its chaperone function.