This limitation is prohibited by proteolytic cleavage of RANKL from the cell surface through the action of MMP-7 and cathepsin G. Importantly, it has been shown in tumor-induced bone disease that soluble RANKL retains its activity and is liberated at the tumor-bone interface promoting osteoclastogenesis without the necessity of direct interaction of osteoblast with osteoclasts [113–115]. The gene discussed is MMP7; the disease is neoplasm.