Therapies targeting DKK1 (BHQ880) are in development for treating MM and SMM.258,259 In this regard, the RANKL inhibitor denosumab has been shown to reduce DKK1 levels.260 Notch signaling has also been implicated in the progression of MM from precursor states through the upregulation of RANKL and alterations in the bone marrow stromal environment.261 To date, bisphosphonate remains one of the standard therapies to reduce the number of osteolytic lesions, ameliorate bone pain, and attenuate pathological fractures and hypercalcemia in MM. The gene discussed is DKK1; the disease is hypercalcemia disease.