RANKRezeptor

RANKRezeptor, commonly referred to as RANK, is a transmembrane receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily. It is encoded by the TNFRSF11A gene in humans. The receptor binds its ligand RANKL (TNFSF11), which is expressed by osteoblasts and other stromal cells, and by activated T cells in certain contexts.

Upon RANKL binding, RANK recruits adaptor proteins of the TRAF family, activating NF-κB, MAPK, and other signaling pathways that drive differentiation and activation of osteoclasts, specialized cells responsible for bone resorption. This signaling is tightly regulated by osteoprotegerin (OPG, encoded by TNFRSF11B), a secreted decoy receptor that binds RANKL and prevents receptor activation.

Expression: RANK is expressed on osteoclast precursors, mature osteoclasts, certain dendritic cells, and subsets of mammary epithelial cells; RANKL is produced by osteoblasts and stromal cells; OPG is produced by osteoblasts and other cells.

Physiological roles: RANK signaling is central to bone remodeling and also participates in immune system development and function, as well as mammary gland development during pregnancy and lactation. In pregnancy, RANK–RANKL signaling promotes alveolar development.

Clinical relevance: dysregulation contributes to osteoporosis and bone metastases in cancer; genetic deficiency leads to osteopetrosis and impaired lymphoid organ development in some models. Therapeutically, targeting the RANK–RANKL axis is established: denosumab is a monoclonal antibody against RANKL used to treat osteoporosis, bone metastases, and hypercalcemia of malignancy; other approaches include osteoprotegerin mimetics and small molecules under investigation.