During the secretory stage, the enamel forming epithelial cells secrete large quantities of protein, including amelogenin, ameloblastin, enamelin and matrix metalloproteinase-20. Together, these proteins form an organic matrix within which thin enamel ribbons of hydroxyapatite crystallize. The pH during the secretory stage of enamel formation is approximately 7.23. Once the enamel ribbons attain their full length, ameloblasts transition to the maturation stage. Exposure to excess F2 can trigger endoplasmic reticulum stress within ameloblasts and compromise protein secretion. Secreted proteins pass through the ER. The ER functions as a quality control organelle and prevents misfolded proteins from traversing the secretory pathway. Factors that adversely affect ER homeostasis cause ER stress and initiate an ER-to-nucleus signaling Segetalin-A pathway, termed the unfolded protein response. Activation of the UPR results in transient attenuation of protein translation, enabling cells to cope with the existing protein load. The UPR also upregulates chaperones, augmenting the folding capacity of the ER. Accumulated proteins may also be removed via the ER-associated degradative pathway. UPR-mediated alleviation of ER stress may allow the cell to survive; prolonged ER stress can result in apoptosis. Enamel formation begins with the Xylitol secretion of enamel matrix proteins during the secretory stage of enamel development. Together, these proteins form a matrix that organizes the hydroxyapatite crystals of the enamel. Once the crystals reach their full length, ameloblasts secrete KLK4 to degrade the matrix proteins, allowing the crystals to grow in width and thickness. The degraded proteins are then resorbed by ameloblasts, leaving behind fully mature, hardened enamel that has a mineral content greater than 96%. Compared to normal enamel, fluorosed enamel has a lower mineral content and a higher protein content and therefore, has reduced hardness. Retention of the matrix proteins is thought to be responsible for the higher protein content of fluorosed enamel.