OCT4 encoded by pou5f1 is one of the most ancient and early transcription factors identified in the embryo. It has been longwise recognized as a gatekeeper for pluripotency of embryonic stem (ES) cell. Uncovered twenty years ago, its fame was built up from its key role in maintaining embryonic stem cell pluripotency in 1998. Since, OCT4 was reported to also instruct stem cell fate through a gene dosage effect. It reached recently a novel glorious hit with its master role in reprogramming somatic cells.