The established structural proteins of the enamel matrix are amelogenin, ameloblastin, and enamelin. Historically, tuftelin and tuftelin-interacting protein 11 (TFIP11) have also been discussed as possible enamel proteins. Protein complexes are achieved by protein–protein interactions, and it is protein complexes that control biomineralization. The purpose of our recent studies was to catalog protein partners for these proteins that are, or have been, implicated in tooth formation. We used the sensitive yeast two-hybrid assay to identify proteins that interact directly with amelogenin, ameloblastin, enamelin, the leucine-rich amelogenin peptide (LRAP) and TFIP11. In this manuscript we refer to, or document, potential protein partners for the proteins listed above. The yeast two-hybrid assay may ultimately prove to be a valuable proteomics methodology for using to decipher molecular events that ultimately result in enamel biomineralization.