Thus, our study not only identifies AR as a bona fide ubiquitination and degradation substrate of SPOP, but also demonstrates that the effect of SPOP on AR degradation is subjected to regulation by physiological and pathological conditions in prostate cancer cells, including SPOP mutation, AR splicing, exposure to androgen, and antiandrogen treatment (Figure 7). The gene discussed is SPOP; the disease is Familial prostate cancer.