B cell-intrinsic RANKK240E drove a fully penetrant systemic lupus erythematosus (SLE)-like disease and facilitated B cell transformation and CLL development, which was not driven by an altered expression of the mutated RANK but rather its aberrant signaling in response to microenvironmental RANKL. The gene discussed is TNFSF11; the disease is B-cell chronic lymphocytic leukemia.