The Protein Disulfide Isomerase (PDI) family is a group of enzymes located in the endoplasmic reticulum, specifically dedicated to protein folding and disulfide bond formation and rearrangement. PDI contains at least one active site capable of catalyzing oxidation-reduction reactions, ensuring proper protein folding. Members of this family are widely distributed in the endoplasmic reticulum and are crucial for maintaining the quality control of intracellular proteins. PDI is expressed in various cell types, and its specific expression and activity regulation influence multiple biological processes, including cellular stress response, immune response, and cell death. Gene mutations or dysregulation in expression are associated with various diseases, such as neurodegenerative diseases, cancer, and rare genetic disorders.