ASCL5 is a bHLH transcription factor that binds E-box motifs, typically in complex with TCF3/E12, and negatively modulates target gene transcription including CDH1 through potential PRC2 recruitment. It plays essential roles in ameloblast development, tooth germ growth, and enamel formation by regulating inner enamel epithelium cell migration. Based on limited published evidence, ASCL5 mutations cause lobodontia, a rare dental anomaly characterized by supernumerary cusps and abnormal molar roots 1. ASCL5 dysregulation affects craniofacial developmental gene expression, including DLX2 activation 1, and may serve as a prognostic marker in pediatric acute myeloid leukemia 2.