Osteoclasts are cells that break down bone; however, excessive bone loss leads to conditions such as osteoporosis. When three proteins called RANKL bind to three receptors called RANK on the osteoclasts’ surfaces, the osteoclasts go to work. Warren et al. linked three mutant versions of RANKL protein together to generate an inhibitor of RANK (see the Perspective by Ou-Yang and Siegel). Two of the proteins bound more strongly to RANK, and the third protein could not bind to RANK. This engineered RANKL variant bound to RANK without activating the receptor, preventing osteoclasts from breaking down bone in mice…
