The formation of enamel's intricate architecture is thought to be rigorously controlled in ameloblasts through interactions of various organic matrix protein molecules that include: enamelin, amelogenin, ameloblastin, tuftelin, dentine sialophosphoprotein, and a variety of enzymes.

Enamelin is thought to be the oldest member of the enamel matrix protein (EMP) family, with animal studies showing remarkable conservation of the gene phylogenetically.

Enamelin has three putative phosphoserines (Ser54, Ser191, and Ser216 in humans) phosphorylated by a Golgi-associated secretory pathway kinase (FAM20C) based on their distinctive Ser-x-Glu (S-x-E) motifs.

[12] At the secretory stage, the enzyme matrix metalloproteinase-20 (MMP20) proteolytically cleaves the secreted enamelin protein immediately upon release, into several smaller polypeptides; each having their own functions.

The primary function of the proteins acts at the mineralisation front; growth sites where it is the interface between the ameloblast plasma membrane and lengthening extremity of crystals.