GBX2 (gastrulation brain homeobox 2) is a homeobox-containing transcription factor that functions as a DNA-binding protein with roles in both normal development and cancer pathogenesis. During embryonic development, GBX2 acts as a candidate control gene for cell pluripotency and differentiation 1, with expression detected in undifferentiated embryonic stem cells and the inner cell mass of preimplantation embryos before being downregulated upon differentiation. The gene encodes a 347-amino acid protein with a conserved homeodomain 2 and is expressed in the developing central nervous system 2. In cancer contexts, GBX2 is consistently overexpressed in prostate and breast cancer cell lines compared to normal tissues 34. GBX2 promotes cancer cell growth through multiple mechanisms: it transcriptionally upregulates interleukin-6 (IL-6) via ATTA motif binding in the IL-6 promoter 5, and activates the Wnt/β-catenin signaling pathway to promote proliferation, invasion, and angiogenesis 6. GBX2 downregulation reduces clonogenic ability by ~50% and tumorigenicity by >70% in xenograft models 4. Additionally, GBX2 expression is regulated post-transcriptionally through the circRERE/miR-1299 axis and N6-methyladenosine modifications in hepatocellular carcinoma 7. Early-life stress induces differential methylation near GBX2, potentially affecting offspring central nervous system development 8.