ERO1B is an endoplasmic reticulum (ER) oxidoreductase that catalyzes disulfide bond formation essential for protein folding. It functions by reoxidizing protein disulfide isomerase (P4HB/PDI), the primary enzyme catalyzing disulfide bond formation, enabling continued rounds of protein disulfide formation 1. Following P4HB reoxidation, ERO1B transfers electrons to molecular oxygen via FAD, generating reactive oxygen species (ROS) in the process. The enzyme preferentially reoxidizes P4HB (100% reference rate) over other PDI family members, with PDIA2 at ~50% efficiency and others at <10% 2. ERO1B plays a critical role in pancreatic beta-cell function, particularly in oxidative proinsulin folding and glucose homeostasis. Genetic variants affecting ERO1B splicing are associated with type 2 diabetes (T2D) susceptibility, with splicing QTLs creating nonsense isoforms that disrupt its role as an ER-stress regulator 1. Recent functional studies confirmed that ERO1B knockdown affects glucose-stimulated insulin secretion in beta cells 2. Proteomic analyses reveal reduced ERO1B expression in prediabetic islets with impaired beta-cell glucose sensitivity, suggesting involvement in early T2D pathogenesis 3. Additionally, ERO1B exhibits causal associations with lung function and appears in prognostic models for various cancers, indicating broader physiological relevance beyond glucose homeostasis 4.