RANK (Receptor Activator of Nuclear Factor Kappa-B), also known as TNFRSF11A, is a member of the tumor necrosis factor receptor superfamily that plays critical roles in bone metabolism, immune cell activation, and has emerging implications in neurodegenerative diseases.
RANK is a human gene whose product rANK is a type I transmembrane protein expressed primarily on osteoclast precursors, dendritic cells, and activated T cells[1]. It serves as the receptor for RANKL (RANK ligand) and plays essential roles in:. Variants in RANK have been implicated in Neurodegeneration, Inflammatory Conditions, Cancer. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
RANK is a type I transmembrane protein expressed primarily on osteoclast precursors, dendritic cells, and activated T cells[1:1]. It serves as the receptor for RANKL (RANK ligand) and plays essential roles in:
RANK shows tissue-specific expression:
In the CNS, RANK expression is elevated in activated microglia surrounding amyloid plaques in AD[5].
| Variant | Function | Associated Phenotype |
|---|---|---|
| A133V | Reduced signaling | Bone density variants |
| K171E | Altered ligand binding | Immunodeficiency |
Anderson DM, Maraskovsky E, Billingsley WL, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. 1997. ↩︎ ↩︎
Hsu R, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. 1999. ↩︎
Josien R, Wong BR, Li HL, Steinman RM, Choi Y. TRANCE, a TNF family member, is differentially expressed on T cell subsets and induces dendritic cell maturation. 1999. ↩︎
Wu K, Byers DE, Jin X, et al. TREM-2 promotes macrophage survival and lung tumor growth. 2020. ↩︎
Liu CC, Hu J, Tsai CW, et al. Microglial RANK contributes to neuronal damage in Alzheimer's disease. 2022. ↩︎