DPPA4 (developmental pluripotency associated 4) is a chr3-binding protein essential for maintaining pluripotency and regulating developmental competency. In pluripotent stem cells, DPPA4 functions as a chr3 modifier that primes and maintains bivalent chr3 domains by regulating H3K4me3 and H3K27me3 histone marks at the transitional boundary between pluripotency and differentiation 1. DPPA4 localizes to both the nucleus, where it associates with active chr3, and the cytosol, where it forms dynamic foci and interacts with proteins involved in mRNA processing and nucleocytoplasmic transport 2. The gene is highly and selectively expressed in pluripotent stem cells and germ cells but becomes downregulated during differentiation and germ line commitment 3. Clinically, DPPA4 overexpression promotes tumor aggressiveness by enhancing cell stemness through WNT/β-catenin signaling in pituitary neuroendocrine tumors 4. DPPA4 variants have been associated with acute radiation-induced toxicity across multiple cancer types, potentially relating to stem cell-mediated tissue repair mechanisms 5. Mutations in DPPA4 are implicated in early embryonic arrest, disrupting embryonic genome activation 6. Additionally, prenatal alcohol exposure decreases DPPA4 DNA methylation, linking this gene to developmental disorders and fetal alcohol spectrum disorder pathogenesis 7.