The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. The luminal components of the insulin SG can be functionally segregated into four groups. These are cargo molecules, luminal enzymes and chaperones, ions (and their transporters and channels), and sorting receptors.