The Research Topic will host an overview of the most recent knowledge on enamel issued from a group of international experts who gathered at the 10th International Symposium on Dental Enamel (Enamel X). The Topic will include manuscripts describing original data, short communication, and reviews. In addition, the Topic will host abstracts and panel discussions presented at the Enamel X meeting, to highlight changing paradigms, unsolved and challenging questions, as well as translational challenges. Bringing together physics, chemistry, biochemistry and development and differentiation, contributions to this Topic will focus on the unique architecture of enamel, from nano- to macro- scale, and the dynamic molecular interactions with lead to extracellular self-assembly and mineralization. This knowledge will open a window into innovative bioinspired treatment and materials for tissue repair and regeneration. Tissue-specific networks and pathways shared with a number of biological systems (clock genes, epithelial polarization/ion handling, cell niche dynamics, and cell signaling) will also be explored. This will give an overall picture of the multiple acellular, cellular and organismal (essentially transgenic mice) processes actively investigated in the enamel field. Similarly, lessons from isolated or syndromic, inherited and acquired enamel defects obtained using cutting edge cell and matrix-omics will establish the emerging genomic framework determining enamel quality. Tooth enamel defects reflect historical and present gene-environment interactions in the animal and human condition such as climate, nutrition, pollutants or fluoride exposures. This last fact is highly relevant in medicine and public health since poor tooth quality and mineral defects are one of the first human worldwide pathologies.