FZD5 (frizzled class receptor 5) functions as a critical Wnt protein receptor that mediates both canonical and non-canonical Wnt signaling pathways across multiple tissues. FZD5 serves as an essential regulator of intestinal homeostasis, where epithelial-specific knockout results in lethal pan-intestinal crypt and villus loss, and depletion specifically in Lgr5+ intestinal stem cells causes premature differentiation 1. The receptor undergoes Wnt-induced endocytosis and degradation through ZNRF3/RNF43-mediated mechanisms, representing a negative regulatory feedback loop 2. In cardiovascular disease, FZD5 mediates cardiac fibrosis through crosstalk with EGFR signaling in response to Wnt5a and Wnt11 under pressure overload conditions 3. FZD5 also plays important roles in angiogenesis, where it mediates VEGF-independent angiogenesis through Wnt5a/FZD5/NF-κB/ERK signaling in breast cancer 4. Additionally, FZD5 contributes to hepatic metabolism by controlling cholesterol uptake and bile acid conjugation in hepatocytes via WNT2 signaling 5, and participates in pulmonary epithelial metaplasia through sFRP2-mediated non-canonical Wnt signaling 6. The receptor shows primate-specific expression patterns during early gastrulation 7 and responds to engineered Wnt surrogate agonists 8.