amelogenin

Amelogenin is the major extracellular matrix protein of dental enamel, secreted by ameloblasts during the secretory stage of amelogenesis. It is a phosphoprotein that self-assembles into nanospheres and scaffolds the organized deposition and subsequent mineralization of hydroxyapatite crystals, guiding enamel prism formation and controlling crystal width and orientation. Amelogenin accounts for the majority of the organic enamel matrix and interacts with other enamel matrix proteins such as enamelin and ameloblastin.

In humans, amelogenin is encoded by AMELX on the X chromosome and, in males, a paralog AMELY on the Y chromosome. The two genes encode highly similar but not identical proteins. Alternative splicing yields multiple amelogenin isoforms, contributing to functional diversity in enamel formation. Mutations in AMELX or AMELY can disrupt enamel formation and result in X-linked or Y-linked amelogenesis imperfecta, characterized by thin, hypoplastic, or hypomineralized enamel.

During maturation, amelogenin is processed by enamel-specific proteases such as MMP20 (enamelysin) and KLK4, generating peptide fragments that regulate the growth and maturation of enamel crystals.

Forensic and evolutionary studies have used amelogenin gene variants for sex determination, and animal models with amelogenin disruption provide insight into enamel formation.