PAX9 is a transcription factor essential for development of multiple tissues including the thymus, parathyroid glands, teeth, and craniofacial skeletal elements 1. During odontogenesis, PAX9 functions as a key regulator orchestrating tooth morphogenesis through reciprocal epithelial-mesenchymal interactions 1. Specifically, PAX9+ progenitor cells contribute primarily to periodontal tissue formation and are spatially organized within developing teeth, working alongside Cd24a+ cells that generate dentin-pulp tissues 2. PAX9 mediates palatogenesis through interactions with multiple signaling pathways including FGF, BMP, WNT/β-catenin, and SHH, regulating palatal shelf elongation, elevation, and fusion 3. Beyond developmental roles, PAX9 functions in cancer biology, where dysregulation through promoter hypermethylation, microRNA modulation, or pathway inhibition contributes to carcinogenesis in head and neck, esophageal, lung, and cervical cancers 4. Clinically, PAX9 mutations cause autosomal-dominant non-syndromic oligodontia and hypodontia, with over 50 mutations reported affecting tooth number, position, and morphology 5. PAX9 gene polymorphisms (rs2073247, rs2073244) significantly increase tooth agenesis risk, particularly in Caucasian populations 6. These findings underscore PAX9's critical roles in craniofacial and dental development, with implications for understanding congenital dental disorders and cancer pathogenesis.