Human Frizzled Homolog 4 (FZD4) Protein

Background

FZD4 is a Wnt receptor that mediates canonical β-catenin-dependent signaling and non-canonical pathways. It is expressed in vascular endothelial cells, the retina, and skeletal tissue, playing a key role in angiogenesis, vascular integrity, and retinal development. FZD4 interacts with Wnt ligands and coreceptors like LRP5/6 to activate β-catenin signaling, which is essential for retinal vascularization and blood-retina barrier maintenance. Mutations in FZD4 are associated with familial exudative vitreoretinopathy (FEVR), a genetic disorder characterized by incomplete retinal vascular development, leading to vision loss. In cancer, FZD4 promotes tumor angiogenesis and metastasis by activating Wnt signaling pathways that support endothelial cell proliferation and survival. Its overexpression has been observed in breast and colorectal cancers, where it enhances angiogenesis and therapy resistance. FZD4 also regulates bone formation and osteoblast differentiation, contributing to skeletal development. Targeting FZD4 and its signaling pathways has therapeutic potential in vascular disorders, cancer, and ocular diseases. Overall, FZD4 is essential for vascular development and maintenance, with dysregulation contributing to angiogenic disorders and tumor progression.