DMBX1 (diencephalon/mesencephalon homeobox 1) is a paired-class homeodomain transcription factor that functions as a transcriptional repressor 1. It forms heterodimers with OTX2 on specific DNA sequences to repress OTX2-mediated transactivation, particularly of p21, thereby regulating cell cycle progression 1. During embryonic development, DMBX1 is expressed in the anterior head folds and becomes restricted to the caudal diencephalon and mesencephalon neuroepithelium, serving as a marker of developing anterior nervous system 2. In normal physiology, DMBX1 plays essential roles in energy homeostasis and feeding behavior 34. Adult DMBX1 expression in the lateral parabrachial nucleus is required for agouti-related peptide's long-lasting orexigenic effects, with Dmbx1 knockout mice exhibiting severe leanness, hypophagia, and hyperactivity 34. Clinically, DMBX1 has emerged as an oncogenic factor across multiple cancers. It is overexpressed in lung adenocarcinoma, hepatocellular carcinoma, and colon cancer, correlating with poorer prognosis and advanced clinicopathological features 156. DMBX1 knockdown inhibits cancer cell proliferation, migration, and invasion while suppressing epithelial-mesenchymal transition markers 56. DMBX1 has been identified as a disease gene in autosomal recessive neurological disorders 78.