BTK plays a key role in the tonic BCR signaling pathway through the positive regulation of AKT phosphorylation (Fig. 1).187 The inhibition of BTK decreased BTKY223 phosphorylation and anti-apoptotic protein expression (BCL-2, BCL-XL, and MCL-1), resulting in increased apoptosis in MCL cell lines.188 Moreover, recurrent gene mutations of the BCR-BTK signaling pathway are frequently found in ABC-DLBCL, FL, and marginal zone lymphoma (MZL).4,189–192. Here, BTK is linked to mantle cell lymphoma.