Pdia3, also known as ERp57, is a member of the protein disulfide isomerase (PDI) family. Its most important characteristic is the catalysis of disulphide (SS) bonds in the endoplasmic reticulum. It acts as a chaperone, is highly expressed in response to cellular stress, and intercepts apoptotic cell death related to endoplasmic reticulum stress and protein misfolding [1].

In adipose tissue, Pdia3 is required for the maintenance of migratory and pro-inflammatory properties of a unique subset of adipose macrophages (iMAMs). Administration of Pdia3 small interfering RNA-loaded liposomes effectively repressed adipose inflammation and high-fat diet-induced obesity, suggesting targeting Pdia3 could be a viable approach against obesity and metabolic disorders [2]. In the context of viral infections like rabies, PDIA3 restricted RABV infection by mediating the degradation of RABV G protein and blocking viral entry into host cells [3]. In autoimmune diseases such as rheumatoid arthritis, pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses, as it facilitates the non-canonical nuclear import of STAT1 and PKM2 in T cells [4].

In conclusion, Pdia3 plays essential roles in various biological processes and disease conditions. Its functions range from chaperoning and regulating disulfide bond formation to influencing cell migration, inflammation, viral infections, and autoimmune responses. Gene knockout or knockdown models in mice have been crucial in revealing these roles, providing potential therapeutic targets for diseases like obesity-related metabolic disorders, viral diseases, and autoimmune diseases.