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Frizzled class receptor 5 and Low-density lipoprotein receptor-related protein 6 (FZD5 and LRP6)
- Target
- FZD5 and LRP6
- Molecular classification
- G protein-coupled receptor, Receptor, Co-receptor, Single-pass membrane protein
01
Overview
Frizzled class receptor 5 (FZD5) and Low-density lipoprotein receptor-related protein 6 (LRP6) act as cell-surface co-receptors essential for initiating canonical Wnt/β-catenin signaling. Upon Wnt ligand binding, FZD5 (a seven-transmembrane G protein-coupled receptor) and LRP6 (a single-transmembrane co-receptor) form a ternary complex that recruits intracellular scaffolding proteins such as Dishevelled and Axin. This leads to inhibition of β-catenin phosphorylation, its stabilization, and subsequent activation of Wnt-responsive gene expression. These receptors are key regulators of embryonic development, stem cell maintenance, and tissue repair, but their dysregulation is implicated in a variety of diseases including cancer and metabolic bone disorders[1][2][3][4][5][6][7].
- Other names
- Frizzled receptor 5 (FZD5)LRP6Frizzled-5Low-density lipoprotein receptor-related protein 6
02
Mechanism of action
Inhibition of ligand (Wnt) binding to prevent pathway activation; Blockade of FZD5–LRP6 interaction to suppress β-catenin stabilization; Antagonism of receptor clustering and phosphorylation events necessary for signal initiation
03
Biological functions
Signal transductionCanonical Wnt/β-catenin signalingRegulation of gene expressionEmbryonic developmentCell proliferationTissue homeostasis
04
Disease associations
CancerBone diseases (e.g., osteoporosis, high bone mass syndromes)Neurodegenerative diseaseCardiovascular disease
05
Safety considerations
Unintended inhibition of Wnt signaling may cause developmental toxicity, impaired tissue regeneration, or bone metabolism disturbances[1][2].Broad pathway inhibition can affect normal stem cell function and tissue homeostasis.Specificity and off-target effects remain challenges for therapeutic development targeting this pathway.
06
Interacting drugs
Currently, there are no widely approved drugs targeting FZD5–LRP6, but various experimental antibodies, peptides, and small molecules modulating Wnt/β-catenin signaling are in development or used in research.
3 more in the full profile.
07
Biomarkers
Elevated nuclear β-catenin (as a marker of pathway activation)Wnt target gene expression signatures (e.g., AXIN2, MYC, CCND1)Mutations in LRP6 linked to bone density phenotypes[4]
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