This review focuses on recent discoveries and delves in detail about what is known about each of the
proteins (
amelogenin, ameloblastin, and
enamelin) and
proteinases (
matrix metalloproteinase-20 and
kallikrein-related
peptidase-4) that are secreted into the enamel matrix. After an overview of enamel development, this review focuses on these enamel
proteins by describing their nomenclature, tissue expression, functions,
proteinase activation, and
proteinase substrate specificity. These
proteins and their respective null mice and human mutations are also evaluated to shed light on the mechanisms that cause nonsyndromic enamel malformations termed
amelogenesis imperfecta. Pertinent controversies are addressed. For example, do any of these
proteins have a critical function in addition to their role in enamel development? Does
amelogenin initiate crystallite growth, does it inhibit crystallite growth in width and thickness, or does it do neither? Detailed examination of the null mouse literature provides unmistakable clues and/or answers to these questions, and this data is thoroughly analyzed. Striking conclusions from this analysis reveal that widely held paradigms of enamel formation are inadequate. The final section of this review weaves the recent data into a plausible new mechanism by which these
enamel matrix proteins support and promote enamel development.