ESR2 and Familial prostate cancer: ERβ-selective agonists have been tested as therapeutic agents in the treatment of prostate cancer, including the most lethal form, CRPC27–31, and because ERβ has tumor suppressor activity, it is frequently downregulated4,7,19,20,27,53,54, partial loss of ERβ correlates with castration resistance2, and such agonists upregulate ERβ expression57.