DLX3 is a homeodomain transcription factor that functions as a transcriptional regulator across multiple developmental and physiological contexts. As a DNA-binding transcription factor, DLX3 recognizes specific DNA sequences and can cooperatively bind DNA with other transcription factors, with structural studies revealing that DNA-mediated interactions often involve overlapping recognition motifs 1. DLX3 positively regulates gene expression in epidermal differentiation and is expressed in differentiating keratinocytes, neural crest, hair follicles, dental epithelium, and placental tissues 2. In placental development, DLX3 coordinates with GCM-1 to regulate placental growth factor expression, though their co-expression antagonizes individual transactivation through physical protein-protein interactions mediated by the DLX3 homeodomain 34. During dentinogenesis, DLX3 functions downstream of BMP signaling to promote odontoblast differentiation and dentin formation 5. In keratinocyte biology, DLX3 regulates p53-dependent epidermal differentiation and may protect against squamous cell carcinogenesis, potentially through neurotrophin-mediated signaling 6. Functionally, DLX3 polymorphisms associate with dental caries susceptibility, with specific alleles conferring protective or risk effects 78. Mutations in DLX3 cause amelogenesis imperfecta 4 and trichodentoosseous syndrome, highlighting its essential role in tooth enamel formation and skeletal development.