Frizzled-5 receptor (FZD5)

The **Frizzled-5 receptor (FZD5)** is a member of the **Frizzled family of G protein-coupled receptors (GPCRs)**, serving as a key receptor for **Wnt proteins**. The protein structure features an extracellular **cysteine-rich domain (CRD)** critical for binding lipid-modified Wnt ligands, a seven-transmembrane (7TM) region, and intracellular signaling domains[1][2][3][4]. FZD5 acts in both **canonical (Wnt/β-catenin)** and **non-canonical (planar cell polarity, calcium pathway)** Wnt signaling cascades, regulating diverse biological functions such as embryonic patterning, stem cell renewal, tissue regeneration, and maintenance of cell polarity[3][4]. Aberrant FZD5 signaling is implicated in various diseases, notably cancers and fibrotic or inflammatory conditions, making it a therapeutic target of ongoing preclinical and early clinical interest[3]. However, no approved drugs directly target FZD5 to date, and therapeutic modulation is challenged by pathway complexity and essential physiological roles.

Other names

FZD5Frizzled class receptor 5Fz-5HZFZ5

Wnt ligand binding to extracellular cysteine-rich domain (CRD) Complex formation with LRP5/6 co-receptors for β-catenin pathway activation (canonical) Activation of planar cell polarity and calcium pathway (non-canonical) Inhibition by secreted antagonists (e.g., sFRPs, DKK proteins)[3][4]