The advent of Bruton tyrosine kinase inhibitors (BTKi) revolutionized the management of patients with B-cell lymphoproliferative diseases (BLPD), especially for chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) and mantle cell lymphoma (MCL). The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.