If not received in the front-line setting, upon progression to the castration-resistant state (CRPC), second-generation potent androgen receptor pathway inhibitors (ARPi) such as abiraterone, enzalutamide, and apalutamide, targeting androgen bio-synthesis and AR-ligand binding, respectively, are routinely used to further inhibit AR-driven cancer progression. The gene discussed is AR; the disease is cancer.