The RANKL/RANK/OPG system plays a critical role in regulating bone resorption and osteoclast formation. RANKL, a member of the tumor necrosis factor (TNF) superfamily, binds to its receptor RANK on osteoclast precursors, promoting their differentiation, activation, and survival. OPG, a soluble receptor that binds RANKL, prevents RANKL from activating RANK, thereby inhibiting osteoclast formation and protecting the skeleton from excessive bone resorption. The balance between RANKL and OPG determines bone mass and skeletal integrity. Genetic studies in mice have shown that RANKL/RANK signaling is essential for lymph node formation, mammary gland lactational hyperplasia, and protection against arterial calcification. RANKL also plays a role in other tissues, such as the mammary gland and bone metastasis. RANKL is expressed in various tissues, including lymph nodes, thymus, and lung, and is involved in inflammatory conditions like rheumatoid arthritis. RANKL promotes the release of immature progenitors into the circulation and is involved in the regulation of bone remodeling and hematopoiesis. RANKL is also expressed in mammary epithelial cells during pregnancy and is required for lactational hyperplasia and milk production. RANKL can be produced by tumor cells and may contribute to tumor cell proliferation. RANK, the receptor for RANKL, is expressed on osteoclasts, mature osteoclasts, and dendritic cells, and is involved in T-cell activation. RANKL/RANK signaling is essential for osteoclast formation and bone remodeling. RANKL/RANK signaling is also involved in the regulation of immune responses and bone disease. OPG is expressed in various tissues, including heart, kidney, liver, spleen, and bone marrow, and its expression is regulated by factors that induce RANKL expression. OPG plays a protective role in bone and vascular diseases. RANKL/RANK signaling is also involved in the regulation of osteoblast function and the anabolic effects of PTH. The RANKL/RANK/OPG system is a key discovery in bone biology and has important implications for skeletal health and disease. However, many questions remain about the roles of these factors in health and disease. The system is also involved in other tissues and may play a role in cardiovascular disease. The RANKL/RANK/OPG system is a complex network that regulates bone remodeling and other physiological processes.The RANKL/RANK/OPG system plays a critical role in regulating bone resorption and osteoclast formation. RANKL, a member of the tumor necrosis factor (TNF) superfamily, binds to its receptor RANK on osteoclast precursors, promoting their differentiation, activation, and survival. OPG, a soluble receptor that binds RANKL, prevents RANKL from activating RANK, thereby inhibiting osteoclast formation and protecting the skeleton from excessive bone resorption. The balance between RANKL and OPG determines bone mass and skeletal integrity. Genetic studies in mice have shown that RANKL/RANK signaling is essential for lymph node formation, mammary gland lactational hyperplasia, and protection against arterial calcification. RANKL also plays a role in other tissues, such as the mammary gland and bone metastasis. RANKL is expressed in various tissues, including lymph nodes, thymus, and lung, and is involved in inflammatory conditions like rheumatoid arthritis. RANKL promotes the release of immature progenitors into the circulation and is involved in the regulation of bone remodeling and hematopoiesis. RANKL is also expressed in mammary epithelial cells during pregnancy and is required for lactational hyperplasia and milk production. RANKL can be produced by tumor cells and may contribute to tumor cell proliferation. RANK, the receptor for RANKL, is expressed on osteoclasts, mature osteoclasts, and dendritic cells, and is involved in T-cell activation. RANKL/RANK signaling is essential for osteoclast formation and bone remodeling. RANKL/RANK signaling is also involved in the regulation of immune responses and bone disease. OPG is expressed in various tissues, including heart, kidney, liver, spleen, and bone marrow, and its expression is regulated by factors that induce RANKL expression. OPG plays a protective role in bone and vascular diseases. RANKL/RANK signaling is also involved in the regulation of osteoblast function and the anabolic effects of PTH. The RANKL/RANK/OPG system is a key discovery in bone biology and has important implications for skeletal health and disease. However, many questions remain about the roles of these factors in health and disease. The system is also involved in other tissues and may play a role in cardiovascular disease. The RANKL/RANK/OPG system is a complex network that regulates bone remodeling and other physiological processes.