The present invention provides methods for identifying agents capable of modulating RANK-mediated signaling pathways. The present invention also provides compositions and methods of using the same to treat osteoporosis or other RANK-related diseases. The present invention is based on the functional and structural analysis of three TRAF-binding motifs (PTM)—namely, PTM3, PTM5, and PTM6, each of which has been found to play a distinct role in the activation of RANK-mediated intracellular signaling. These PTMs can be used to screen for RANK modulators. These PTMs also represent potential drug targets for diseases that are associated with abnormal RANK expression or activity.
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