To elucidate the role of ZDHHC2 in the enzalutamide response in spontaneous prostate cancer models, we established a ZDHHC2 knockout (KO) mouse model through CRISPR/Cas‐mediated genome engineering (Figure S2A, Supporting Information) and verified ZDHHC2 KO via PCR and western blotting (Figure S2B–D, Supporting Information). Here, ZDHHC2 is linked to Familial prostate cancer.