Second‐generation androgen receptor (AR) antagonists, particularly enzalutamide (ENZ), have become the cornerstone of advanced prostate cancer management, spanning biochemical recurrence to castration‐resistant prostate cancer (CRPC).[1, 2] While recent trials demonstrated efficacy of ENZ in metastatic hormone‐sensitive prostate cancer (mHSPC),[3, 4] therapeutic resistance inevitably emerges, with median progression‐free survival limited to 33 months.[3] Therefore, unraveling mechanisms underlying acquired ENZ resistance thus represents a pressing clinical priority. The gene discussed is AR; the disease is prostate cancer.