TGIF2LX is an X-linked homeodomain transcription factor that functions as a tumor suppressor in colorectal cancer through transcriptional regulation. The protein demonstrates DNA-binding transcription repressor activity and negatively regulates cell proliferation and angiogenesis 1. In functional studies, TGIF2LX overexpression significantly inhibited cell growth in both in vitro colon adenocarcinoma models and in vivo Drosophila tissues, with growth inhibition partially rescued by Myc or Cyclin E co-expression 12. The protein regulates specific target genes involved in morphogenesis, including downregulation of Nir1 and upregulation of Nir2 and FHIT genes 34. TGIF2LX also modulates long non-coding RNAs ROR and XIST expression in colorectal cancer cells 5. Clinical significance is evidenced by significantly reduced TGIF2LX expression in colorectal cancer tissues compared to normal tissues, suggesting its role as a tumor suppressor 5. The gene shows testis-specific expression in normal tissues and has been identified as a cancer testis antigen in non-small cell lung cancer 6. Additionally, genetic variants near TGIF2LX have been associated with metopic craniosynostosis risk 7.