The PDIA3 protein is a thiol oxidoreductase that has protein disulfide isomerase activity. PDIA3 is also part of the major histocompatibility complex (MHC) class I peptide loading complex, which is essential for formation of the final antigen conformation and export from the endoplasmic reticulum to the cell surface. This protein of the endoplasmic reticulum interacts with lectin chaperones such as calreticulin and CNX in order to modulate the folding of proteins that are newly synthesized. It is believed that PDIA3 plays a role in protein folding by promoting the formation of disulfide bonds, and that CNX facilitates the positioning substrates next to the catalytic cysteines. This function allows it to serve as a redox sensor by activating mTORC1, which then mediates mTOR complex assembly to adapt cells to oxidative damage. Thus, PDIA3 regulates cell growth and death according to oxygen concentrations, such as in the hypoxic microenvironment of bones. Additionally, PDIA3 activates cell anchorage in bones by associating with cell division and cytoskeleton proteins, such as beta-actin and vimentin, to form a complex which controls TUBB3 folding and proper attachment of the microtubules to the kinetochore. PDIA3 also plays a role in cytokine-dependent signal transduction, including STAT3 signaling.PDIA3 may also participate in Vitamin D (specifically, calcitriol) signaling as a membrane-bound receptor.