A quest for clarity in bone erosion: The role of sequestosome 1 in Paget's disease of bone

Alterations in the SQSTM1 gene are a putative cause of Paget's disease of bone, yet results are conflicting about how these mutations impact osteoclasts, the cell type believed to be the main pathological contributor. In this issue of JBC, Zach et al. provide important new evidence that the protein encoded by SQSTM1, p62, negatively regulates osteoclastogenesis and demonstrate that aged p62-deficient mice develop bone phenotypes similar to those of Paget's disease. These findings help to clarify the role of this important protein and present new opportunities to interrogate bone biology.