Osteolysis, a clinical hallmark of multiple myeloma, results from changes in several intra- and intercellular pathways such as RANK/RANKL/osteoprotegerin, Notch, Wnt, RUNX2, EphrinB2/EphB4, and the TNF pathway, involving signaling molecules such as Dickkopf-1 (DKK1), sclerostin, periostin, osteopontin, growth factor independence-1 (GFI1), bone morphogenetic proteins, TGF-β, activin A, annexin II, adiponectin, Bruton's tyrosine kinase (BTK), stromal cell-derived factor-1α (SDF-1α), chemokines, and interleukins [109]. The gene discussed is BTK; the disease is plasma cell myeloma.