In the present study, we characterize that nuclear receptor ERRα, which displays an up-regulation in prostate cancer and a further increase in PCSCs, can directly target and transrepress ZIP1 and through this ERR-mediated down-regulation of ZIP1, ERRα significantly prevents the Zn uptake and accumulation in the isolated PCSCs independent of their AR expression status. The gene discussed is ESRRA; the disease is prostate cancer.