DOC2B is a calcium-dependent vesicle priming protein that positively regulates SNARE-mediated exocytosis through calcium-dependent phospholipid binding 1. Its tandem C2 domains enable calcium-dependent membrane interactions and can induce membrane hemifusion and tethering 2. DOC2B is critical for glucose-stimulated insulin secretion in pancreatic β-cells 3 and participates in neurotransmitter release in neuronal cells. Beyond exocytosis, DOC2B exhibits cytoprotective functions in β-cells by attenuating proinflammatory signaling. DOC2B enrichment suppresses cytokine-induced CXCL10 expression by reducing IKKβ and STAT-1 activation 45, protecting β-cells from stress-induced dysfunction. Type 1 diabetic individuals show substantial DOC2B deficiency in both pancreatic islets and platelets 6, establishing DOC2B as a potential biomarker of β-cell loss. Additionally, DOC2B is packaged into extracellular vesicles by β-cells via its tandem C2 domains, contributing to the β-cell secretome 3. Beyond metabolic functions, DOC2B negatively regulates Wnt/β-catenin signaling in cervical cancer 7. In neurological disease, DOC2B stability depends on its binding partner Munc18-1; mutations causing STXBP1 encephalopathies destabilize DOC2B and impair synaptic targeting 8, suggesting DOC2B dysfunction contributes to neurological phenotypes.