Androgen receptor (AR) suppresses DPYSL5, and overexpression of DPYSL5 promotes prostate cancer cell plasticity via EZH2-mediated PRC2 activation, suggesting that the AR/DPYSL5/EZH2/PRC2 axis may act as a driver of treatment-induced neuroendocrine prostate cancer. Here, DPYSL5 is linked to prostate carcinoma.