Frizzled class receptor 4 (FZD4) (FZD4)

Frizzled-4 (FZD4) is a seven-transmembrane spanning protein belonging to the Frizzled family of G protein-coupled receptors (UniProt: Q9ULV1). It acts as a receptor for Wnt proteins and the non-Wnt ligand Norrin (NDP), playing a pivotal role in the canonical Wnt/beta-catenin signaling pathway (NCBI Gene: 8322). This pathway is essential for vascular development, particularly in the retina and inner ear, where FZD4-mediated signaling ensures proper blood vessel formation and blood-retina barrier integrity (PubMed: 11553327). Mutations in FZD4 are strongly associated with familial exudative vitreoretinopathy (FEVR), a condition leading to vision loss due to incomplete retinal vascularization (PubMed: 15197484). In the context of oncology, FZD4 is frequently upregulated in various solid tumors, including colorectal and breast cancers, where it contributes to tumor progression, stemness, and chemoresistance (PubMed: 22810588). Therapeutic strategies targeting FZD4 include bispecific antibodies like SZN-413, which aim to activate the pathway for regenerative purposes in retinal diseases, while antagonistic approaches are explored for cancer treatment (PubMed: 35922513).

Other names

Frizzled-4Fz-4Fz4CD344Exudative vitreoretinopathy 1EVR1FEVR

Agonism of the FZD4/LRP5 complex to stimulate canonical Wnt signaling for vascular repair or antagonism to inhibit tumor growth (PubMed: 35922513).