PDIA3 (Protein Disulfide Isomerase Family A Member 3), also known as ERp57 or GRP58, is a multifunctional enzyme belonging to the protein disulfide isomerase (PDI) family. It is predominantly located in the endoplasmic reticulum (ER) and acts as a molecular chaperone and redox catalyst. PDIA3 interacts with lectin chaperones like calreticulin and calnexin to facilitate the folding of newly synthesized glycoproteins by promoting the formation of disulfide bonds. Additionally, it prevents protein aggregation and plays a role in the unfolded protein response (UPR) during ER stress. Beyond its canonical functions, PDIA3 has been implicated in various biological processes, including viral infections, where it can influence viral entry and replication. In disease contexts, PDIA3 is often upregulated in cancers and has been associated with tumor progression and drug resistance. Recent studies also highlight its involvement in metabolic disorders, such as obesity, by regulating the function of adipose tissue macrophages.