Receptor activator of nuclear factor-κB ligand(RANKL),a transmembrane protein of the tumor necrosis factor(TNF) superfamily cytokine, currently provides a paradigm that enables the molecular understanding of the linkage among bone metabolism, organization of lymphoid tissues, establishment of the thymic microenviroment, thermoregulation, metabolic regulation, mammary gland development and tumorigenesis. Here we summarize the recent progress in the understanding of RANKL biology by focusing on the investigation of RANKL expressing cells/organs, signaling and related diseases in the context of the newly established interdisciplinary field of osteonetwork. The elucidation of both physiological and pathological RANKL function will provide a scientific basis for future therapeutic approaches to several RANKL-related diseases.