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During mammalian tooth formation, two proteinases are secreted by ameloblasts: enamelysin (MMP-20) and kallikrein-4 (KLK4). Enamelysin is the early protease. It is expressed by ameloblasts throughout the secretory stage and part of the maturation stage. 1–3 KLK4 is the late protease; its expression by ameloblasts begins in the transition stage and continues throughout enamel maturation. 4 5 Expression of these two proteases overlaps during the transition and early maturation stages, when the bulk of the organic matrix component is removed from the enamel layer. Because of its early pattern of expression, its ability to generate the same pattern of amelogenin cleavages in vitro as those observed in vivo, 6 and the nature of the dental phenotype in enamelysin knockout mice, 7 MMP-20 cleavages are thought to play important roles in crystal elongation, proper formation of the dentino–enamel junction (DEJ …