TNFRSF11A encodes RANK (receptor activator of nuclear factor-κB), a TNF receptor superfamily member essential for bone homeostasis and immune regulation. As the primary receptor for RANKL/TNFSF11, TNFRSF11A is critical for osteoclast differentiation and activation through NF-κB and MAPK signaling pathways 1. Beyond skeletal biology, TNFRSF11A regulates intestinal epithelial homeostasis during pregnancy and lactation by protecting gut epithelial cells from apoptosis and controlling intestinal stem cell niches via BMP signaling, with offspring consequences for metabolic health 2. In immune contexts, TNFRSF11A participates in T-cell and dendritic cell interactions and, when aberrantly activated, cooperates with oncogenic signals to drive B-cell malignancies including chr18 lymphocytic leukemia and multiple myeloma 3. Gain-of-function TNFRSF11A mutations cause skeletal disorders including familial expansile osteolysis, early-onset Paget disease, and juvenile Paget disease characterized by excessive bone remodeling 45. Loss-of-function mutations result in osteopetrosis with increased bone density 5. TNFRSF11A also contributes to asthma pathogenesis through RANKL-RANK axis amplification of airway remodeling via TGFβ1/STAT3 signaling, with therapeutic potential for denosumab-based intervention 6. Additionally, TNFRSF11A expression in macrophages influences inflammatory responses and tissue injury in chr18 kidney disease 7.