OC differentiation (osteoclastogenesis), from myeloid precursors, is driven by two main cytokines; macrophage colony-stimulating factor (M-CSF) and receptor activator of NFκ-B ligand (RANKL).1 Expression of RANK, the corresponding receptor for RANKL, is essential for osteoclastogenesis, with RANK/- mice exhibiting profound osteopetrosis, resulting from a complete lack of OCs.2 The gene discussed is TNFSF11; the disease is osteopetrosis.