RANKL/RANK 

Receptor activator of NF-κB (RANK) and its ligand receptor activator of NF-κB ligand (RANKL) are encoded, respectively, by the Tumor necrosis factor receptor superfamily member 11A (Tnfrsf11a) and the Tumor necrosis factor ligand superfamily member 11 (Tnfsf11) genes, RANK and RANKL constitute a receptor-ligand pair initiating a signaling pathway of paramount relevance in bone remodeling, lymph node formation, establishment of the thymic microenvironment, mammary gland development during pregnancy, and bone metastasis in cancer. RANK mutant mice, as well as RANKL mutant mice, exhibit severe osteopetrosis and defective tooth eruption due to a complete lack in osteoclast. Moreover, RANKL and RANK mutant mice lack lymph nodes and AIRE⁺ thymic medullary epithelial cells.