TBX22 is an X-linked T-box transcription factor that serves as a major genetic determinant crucial for human palatogenesis and craniofacial development 1. The gene encodes a transcriptional regulator containing a truncated T-domain missing 20 amino acids relative to other T-domains 2. TBX22 functions as a transcriptional regulator involved in developmental processes, with expression patterns highly restricted to palate and tongue development 3. During human development, TBX22 is expressed in palatal shelves prior to their elevation above the tongue, in the tongue base corresponding to the frenulum region, and in the nasal septum and tooth buds 4. Mutations in TBX22 cause X-linked cleft palate with ankyloglossia (CPX), a semidominant disorder affecting secondary palate formation 1. The disease results from complete loss of TBX22 function through various mutation types including nonsense, splice-site, frameshift, and missense mutations 1. Novel mutations continue to be identified in different populations, including splice site and missense mutations in Chinese families 5. However, TBX22 mutations are not a major cause of isolated ankyloglossia in some populations 6.