The frizzled gene, originally identified in Drosophila melanogaster, is involved in the development of tissue polarity. The mammalian homolog of frizzled, as well as several secreted mammalian frizzled-related proteins (FRPs), have been described. The frizzled proteins contain seven transmembrane domains, a cysteine-rich domain in the extracellular region and a carboxy-terminal Ser/Thr-xxx-Val motif. They function as receptors for Wnt and are generally coupled to G proteins. The frizzled-5 protein is believed to be the receptor for the Wnt-5A ligand. The cysteine-rich domain of frizzled-8 blocks endogenous Wnts and the effects of Wnt-1 and Wnt-5 on proliferation. The mouse frizzled-8 gene, which encodes a Wnt receptor, is a potent cancer-associated activator of the ∫-catenin-TCF pathway. The frizzled-8 gene contains no introns. Frizzled-8 mRNA has been detected in fetal brain and kidney, and also in adult pancreas, skeletal muscle, kidney and heart. Frizzled is highly expressed in HeLa S3 (cervical uterus cancer) cells and A549 lung cancer cells.