EZHIP

EZHIP, full name EZH2 inhibitory protein, has aliases including CATACOMB and CXorf67. It is a conserved epigenetic regulator that binds EZH2 to suppress PRC2 methyltransferase activity, mimicking H3K27M mutation effects to reduce global H3K27me3 levels. It modulates embryonic epigenetic programming by maintaining parental H3K27me3 asymmetry and regulates gametogenesis via PRC2-mediated gene silencing.
EZHIP overexpression drives diffuse midline glioma and PFA ependymoma in children, correlating with poor prognosis, and its deficiency impairs female fertility. Metformin downregulates EZHIP to inhibit PFA tumor growth in preclinical studies. Sulfonylated viriditoxin derivatives target EZHIP to reverse PRC2 inhibition, showing potent anti-glioma activity in vitro, with relevant preclinical research ongoing for clinical translation.