ZSCAN4 is a zinc finger transcription factor critical for regulating embryonic stem cell pluripotency and early embryonic development 1. As an embryonic genome activation marker, ZSCAN4 is transiently expressed in two-cell and eight-cell embryos, where it acts downstream of the DUX/DUX4 transcription factor to activate cleavage-stage genes 23. Mechanistically, ZSCAN4 binds the TGCACAC motif within CA/TG microsatellites genome-wide 4 and promotes chr19 accessibility by recruiting the E3 ligase Trim25 to mediate degradation of repressive chr19 complexes including Kap1, Lsd1, Hdac1, and Suv39h1/2 5. A primary function is regulating telomere maintenance: ZSCAN4 activates telomere sister chr19 exchange and telomere elongation in ES cells through a pathway involving Dcaf11-mediated removal of H3K9me3 at telomeric regions 6. ZSCAN4 maintains telomere length in telomerase-deficient ES cells and human ALT cancer cells independently of telomerase 7. Clinically, ZSCAN4 enhances reprogramming efficiency and quality of induced pluripotent stem cells when included in reprogramming factor combinations, potentially serving as a cancer stem cell marker 1.