LHX9 (LIM homeobox 9) is a transcription factor primarily known for its role in gonadal development 1. As a DNA-binding protein with sequence-specific double-stranded DNA binding activity, LHX9 functions as an RNA polymerase II-specific transcription factor. During embryonic development, LHX9 is expressed in multiple brain regions, particularly in the developing pineal gland, where it is essential for early pineal gland formation 1. Deletion of Lhx9 in mice results in pineal hypoplasia and causes postnatal hydrocephalus in approximately 70% of mutants by 5-8 weeks of age, indicating LHX9 contributes to maintaining normal brain structure 1. In gonadal development, LHX9 is expressed as a coelomic epithelial marker and is downregulated during the transition to supporting gonadal cell differentiation 2. Beyond developmental roles, LHX9 has emerged as a tumor suppressor. In gliomas, LHX9 expression is decreased, and it functions as a p53-binding protein that inhibits cancer progression by suppressing glycolysis through downregulation of PGK1 3. In gastric cancer, LHX9 expression is elevated and promotes tumor progression through PKM2-mediated glycolytic reprogramming in cancer stem cells 4. Additionally, LHX9 provides neuroprotection to embryonic midbrain and striatal neurons against oxidative stress-induced DNA damage 5. These functions establish LHX9 as a multifunctional transcription factor with critical roles in development, neuroprotection, and cancer biology.