MMP20 (matrix metallopeptidase 20) is a secreted zinc-dependent metalloendopeptidase essential for dental enamel formation through its proteolytic activity 1. The enzyme degrades amelogenin, the primary enamel matrix protein, and extracellular matrix components including aggrecan and COMP, facilitating enamel hardening and maturation 2. MMP20 serves multiple critical functions beyond protein degradation: it promotes ameloblast retreat during enamel thickening, releases intercellular protein stores into the matrix, and maintains enamel-dentin adhesion 1. Functionally, MMP20 works with kallikrein-related peptidase 4 (KLK4) in overlapping and complementary roles; deficiency in either proteinase causes enamel structural defects with increased fragility 1. Clinically, biallelic MMP20 mutations cause amelogenesis imperfecta, a heritable disorder affecting enamel formation in all teeth 3. Notably, heterozygous mutations combined with KLK4 heterozygosity produce unexpected enamel defects, suggesting digenic effects in disease pathogenesis 1. Beyond dentition, MMP20 participates in extracellular matrix organization and shows roles in oral cancer pathogenesis, where DSPP-MMP20 silencing reduces cancer stem cell markers and increases chemotherapy sensitivity 4. Gene expression profiling of enamel renal syndrome demonstrates MMP20 upregulation alongside biomineralization genes, suggesting involvement in ectopic calcification prevention 5.