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-9 gene is located within the Williams Syndrome common deleted region at chromosomal band 7q11.23. Heterozygous deletion of the frizzled-9 gene may contribute to the Williams Syndrome phenotype. In mouse, frizzled-9 overexpression can induce the hyperphosphorylation and relocalization of Dvl-1 from the cytoplasm to the cell membrane and cytosolic beta-catenin accumulation. In rat, frizzled-9 is important in Wnt/beta-catenin signaling in 293T cells. Frizzled-9 is expressed predominantly in brain, testis, eye, skeletal muscle, and kidney.