PDIA3 (protein disulfide isomerase family A member 3) is a multifunctional chaperone protein primarily localized to the endoplasmic reticulum (ER) that catalyzes disulfide bond formation, isomerization, and reduction in client proteins 1. As a core component of the MHC class I peptide loading complex, PDIA3 functions as an essential folding chaperone for TAPBP, facilitating dynamic assembly of MHC I complexes with high-affinity antigens and enabling antigen presentation to cytotoxic T cells 2. PDIA3 expression is upregulated during ER stress and apoptosis, with elevated expression observed in approximately 70% of cancers 1. In viral defense, PDIA3 restricts rabies virus infection by mediating glycoprotein degradation via selective autophagy and blocking viral entry through competitive binding to NCAM1 3. Conversely, PDIA3 surface expression facilitates entry and replication of multiple viruses 1. In cancer, PDIA3 downregulation suppresses acute myeloid leukemia cell proliferation and invasion through MAPK pathway inhibition 4, while elevated PDIA3 correlates with immune infiltration in gliomas and associates with breast cancer risk 56. Additionally, PDIA3-specific immune autoreactivity contributes to hepatic damage in metabolic disorders 7. CD8+ T cell PDIA3 editing enhances anti-tumor immunity 8.