AR and Familial prostate cancer: Since longer polyQ sequences protect against prostate cancer [26, 27] and lead to lower transcriptional activity [28–30] (Fig 3), it appears that the optimal length of the polyQ sequence may be the result of a trade-off between preventing over-activation of AR (if polyQ is too short) and minimizing the possibility of aggregation that leads to neurodegeneration (if polyQ is too long) [35, 47].