Receptor activator of nuclear factor-κB (RANK) is an essential mediator for osteoclast development and diseases associated with mutations at this locus include familial expansile osteolysis and autosomal-recessive osteopetrosis, pointing at a role for the RANK ligand–RANK signaling pathway in the differentiation of embryo-derived macrophages. The gene discussed is TNFRSF11A; the disease is autosomal recessive osteopetrosis.