First‐generation CENPE inhibitors (e.g., GSK923295, PF‐2771) have reached phase I with tolerable myelosuppression, and nanomolar CREB1 blockers such as 666‐15—or forthcoming PROTAC degraders—make the CREB1‐CENPE axis pharmacologically tractable in ccRCC. This evidence concerns the gene CENPE and nonpapillary renal cell carcinoma.