The secreted cytokine RANKL (Receptor Activator of Nuclear factor kappa-B Ligand) is critically involved in osteoclastic differentiation and activation and in the regulation of specific immunity. RANKL exists as a homotrimer, is glycosylated, and occurs in 3 forms: cell-bound RANKL, which is expressed by osteoblast lineage cells, soluble RANKL (sRANKL), which is expressed by activated T lymphocytes, and a truncated ectodomain form derived from the cell-bound RANK Ligand, which is enzymatically processed by TACE (TNF-alpha converting enzyme (TACE; ADAM-17)). All three forms stimulate their specific receptor, RANK, which is located on osteoclastic and dendritic cells. RANKL binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. RANKL augments the ability of dendritic cells to stimulate naive T-cell proliferation. It may be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. It may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis. RANKL is highly expressed in thymus and lymph nodes, but not in non-lymphoid tissues and is abundantly expressed in T-cells but not in B-cells. A high level expression is also seen in the trabecular bone and lung. Recombinant Mouse soluble RANKL is approximately 19.9 kDa and contains 174 amino acids.