DUXB is a double homeobox transcription factor unique to eutherian mammals that functions as a DNA-binding regulator of early embryonic development. As a PRD-like homeodomain protein, DUXB acts as a transcriptional repressor with sequence-specific DNA-binding activity 1. DUXB is transiently expressed during zygotic genome activation (ZGA), the critical transition when embryonic genes are first activated during preimplantation development 23. Mechanistically, DUXB participates in regulating genes essential for embryo genome activation and preimplantation embryo development, showing distinct target gene overlap with other DUX family members 1. Unlike the cytotoxic DUX4, DUXB lacks inherent transcriptional activation potential but shares DNA-binding properties with other DUX proteins 4. DUXB's loss or dysfunction is associated with early embryonic arrest (EEA), a major cause of infertility affecting 40% of ART patients, highlighting its critical role in normal embryonic development 3. When misexpressed outside its normal developmental window, DUX family members including DUXB are implicated in cancer pathogenesis, suggesting that tight temporal regulation of DUXB expression is essential for preventing inappropriate cellular reprogramming 5. These findings establish DUXB as a key regulator of embryonic genome activation with significant implications for reproductive medicine and cancer biology.