Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Other protein disulfide isomerase family members can also be reoxidized, but at lower rates compared to P4HB, including PDIA2 (50% of P4HB reoxidation rate), as well as PDIA3, PDIA4, PDIA6 and NXNDC12 (<10%). Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell. May be involved in oxidative proinsulin folding in pancreatic cells, hence may play a role in glucose homeostasis. Glutathione may be required to regulate its activity in the endoplasmic reticulum. Homodimer; disulfide-linked. Heterodimer with ERO1A; disulfide-linked. Also detected as monomer. Homodimers may be somewhat less active than monomers. Interacts with P4HB. Interacts with ERP44. The association with ERP44 may be essential for its retention in the endoplasmic reticulum. Highly expressed in the digestive tract, including the duodenum and lower digestive tract. In the stomach, highly expressed in enzyme-producing chief cells (at protein level). In the pancreas, expressed in islets of Langerhans and, at lower levels, in enzyme-secreting cells (at protein level). Detected at low level in many other tissues. Up-regulated by inducers of the unfolded protein response (UPR). N-glycosylated. The Cys-90/Cys-95 and Cys-393/Cys-396 disulfide bonds constitute the redox-active center. The Cys-90/Cys-95 disulfide bond accepts electron from P4HB and funnel them to the active site disulfide Cys-393/Cys-396. The Cys-81/Cys-390 disulfide bond may be critical for structural stability. Two long-range disulfide bonds participate in loose feedback regulation. The Cys-90/Cys-130 disulfide bond may be the predominant regulatory switch to modulate the catalytic activity, while the Cys-100/Cys-262 disulfide bond may play an auxiliary regulatory role. Belongs to the EROs family.