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, FRP-1 (also designated SARP2), FRP-2 (also designated SARP1), FRP-3, FRP-4 and SARP3 (also designated FRP-5), have been identified. The Frizzled proteins contain seven transmembrane domains, a cysteine-rich domain in the extracellular region and a carboxy terminal Ser/Thr-xxx-Val motif, and they function as receptors for Wnt. The Frizzled-1 gene maps to human chromosome 7q21 and is expressed in adult heart, placenta, lung, kidney, pancreas, prostate and ovary and in fetal lung and kidney. Frizzled-2 is expressed in adult heart and fetal brain, lung and kidney. The frizzled related proteins FRP-1, FRP-2, FRP-3, FRP-4 and SARP3 are secreted proteins that contain regions of homology to the cysteine-rich ligand-binding domain of frizzled and a conserved hydrophilic carboxy terminal. The gene encoding human SARP3 maps to chromosome 4q31.3 and is expressed in retinal pigment epithelium (RPE) and pancreas, while expression of FRP-1,2 and 4 is high in developing tissues. The FRPs/SARPs are involved in the Wnt signaling pathway by regulating the intracellular levels of b-catenin.