Zytotic genome activation (ZGA) is the first and most critical transition event from the maternal genetic to the embryonic genetic program and the major burst of ZGA occurs only in the late 2-cell stage. ZSCAN4 encodes a SCAN domain and four zinc finger domains and is expressed in late 2-cell embryos and embryonic stem cells. Loss-of-function studies using siRNA shows delays in the progression from the 2-cell to the 4-cell stage and subsequent embryo development. ZSCAN4 plays an important role in the preimplantation development. Also, ZSCAN4 is involved in telomere maintenance and long term genomic stability in ES cells, suggesting that ZSCAN4 may be of critical importance in maintaining pluripotency in replicating stem cells.