Free soluble RANKL (sRANKL) is the circulating form of Receptor Activator of Nuclear Factor Kappa-B Ligand, a member of the TNF superfamily that plays a central role in bone metabolism and immune regulation. RANKL exists in both membrane-bound and soluble forms and binds to its receptor RANK on osteoclast precursors, promoting their differentiation, activation, and survival. Osteoprotegerin (OPG) acts as a decoy receptor, binding RANKL and preventing it from interacting with RANK, thus modulating bone resorption.
In clinical settings, free soluble RANKL is a key biomarker in conditions characterized by abnormal bone turnover, such as osteoporosis, rheumatoid arthritis, and bone metastases. Elevated levels may reflect increased osteoclast activity and bone resorption, and the RANKL/OPG ratio is often used as an index of skeletal remodeling status. Monitoring sRANKL can help assess disease activity and therapeutic response, particularly in anti-resorptive treatments like denosumab, which directly targets the RANKL pathway.
In research contexts, sRANKL is studied for its broader roles in immunity and cancer. It contributes to T-cell activation, dendritic cell function, and the tumor microenvironment. Measurement of sRANKL in serum or plasma samples is common in studies exploring the molecular mechanisms of bone-immune interactions (osteoimmunology), the impact of inflammatory cytokines on bone, and the development of targeted biologics. Its quantification is typically done using ELISA or multiplex immunoassays for high-throughput research applications.
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