Umbralisib, a selective PI3Kδ and casein kinase-1ε (CK1ε) inhibitor, has a different chemical structure and a more favorable safety profile than other PI3K inhibitors (PiK3is); this has enabled its use in combination regimens in clinical trials in first-line and relapsed/refractory CLL. Here, PIK3CD is linked to B-cell chronic lymphocytic leukemia.