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.
Pathway Diagram
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RANK (TNFRSF11A)
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.
Pathway Diagram
Mermaid diagram (expand to render)
Gene Overview
<div class="infobox infobox-gene"> | Property | Value | |----------|-------| | Gene Symbol | RANK (TNFRSF11A) | | Full Name | TNF Receptor Superfamily Member 11A | | Chromosomal Location | 18q21.33 | | NCBI Gene ID | 26986 | | OMIM | 603799 | | Ensembl | ENSG00000141655 | | UniProt | Q9Y275 | | Associated Diseases | Osteoclastogenesis, Paget's disease, bone metastasis, rheumatoid arthritis, neuroinflammation | </div>
Overview
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[@anderson1997]. 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.
Normal Function
RANK is a type I transmembrane protein expressed primarily on osteoclast precursors, dendritic cells, and activated T cells[@anderson1997]. It serves as the receptor for RANKL (RANK ligand) and plays essential roles in:
Bone Metabolism
Osteoclast Differentiation: RANKL binding activates [NF-κB](/entities/nf-kb), c-Fos, and NFATc1 signaling cascades that drive osteoclast precursor cells to mature, functional osteoclasts[@hsu1999]
Bone Remodeling: The RANK/RANKL/OPG axis is the primary regulator of bone resorption and formation balance
Alzheimer's Disease: RANK-mediated microglial activation contributes to chronic neuroinflammation in AD brains. RANKL can induce pro-inflammatory cytokine production from microglia[@wu2020]
Parkinson's Disease: The RANK/RANKL system may modulate neuroinflammation in PD pathogenesis
Amyotrophic Lateral Sclerosis: Altered RANK expression has been observed in ALS models
Inflammatory Conditions
Rheumatoid Arthritis: Hyperactive RANK signaling drives excessive bone erosion
Inflammatory Bowel Disease: RANK contributes to intestinal inflammation
Cancer
Bone Metastases: Many cancers exploit RANK signaling for bone metastasis
Multiple Myeloma: RANK is critical for myeloma cell survival in bone marrow
Expression Pattern
RANK shows tissue-specific expression:
High Expression: Bone marrow, lymph nodes, spleen, thymus
[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)](https://pubmed.ncbi.nlm.nih.gov/9367155/)
[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)](https://pubmed.ncbi.nlm.nih.gov/10097072/)
[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)](https://pubmed.ncbi.nlm.nih.gov/10072493/)
[Wu K, Byers DE, Jin X, et al, TREM-2 promotes macrophage survival and lung tumor growth (2020)](https://pubmed.ncbi.nlm.nih.gov/31826923/)
[Liu CC, Hu J, Tsai CW, et al, Microglial RANK contributes to neuronal damage in Alzheimer's disease (2022)](https://doi.org/10.1038/s41593-022-01023-7)
Pathway Diagram
The following diagram shows the key molecular relationships involving RANK (TNFRSF11A) discovered through SciDEX knowledge graph analysis: