Afterwards, PDI can be regenerated to its oxidized form in the endoplasmic reticulum by transferring electrons to reoxidizing proteins such ER oxidoreductin 1 (Ero 1), VKOR (vitamin K epoxide reductase), glutathione peroxidase (Gpx7/8), and PrxIV (peroxiredoxin IV).

[11] For the reductase method, a misfolded substrate disulfide bond is converted to a pair of reduced cysteine residues by the transfer of electrons from glutathione and NADPH.

For the isomerase method, intramolecular rearrangement of substrate functional groups is catalyzed near the N terminus of each active site.

Protein disulfide-isomerase has also been suggested to play a role in the formation of regulatory disulfide bonds in chloroplasts.

[12] Protein disulfide-isomerase helps load antigenic peptides into MHC class I molecules.

Yet conflicting studies have shown that it is not available on the cell surface, but instead is found in significant amounts in the blood plasma.

[4] These signals can also inactivate translation of these misfolded proteins, because the cascade travels from the ER to the nucleus.

Such adverse changes in the normal cellular environment of susceptible cells, such as neurons, leads to nonfunctioning thiol-containing enzymes.

[19] It has been shown that protein disulfide-isomerase activity is inhibited by red wine and grape juice, which could be the explanation for the French paradox.