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Vertebrate proteins activate several distinct pathways. Intrinsic differences among ligands and Frizzled receptors, and the availability of pathway-specific co receptors. A secreted glycoprotein, Cthrc1, is involved in selective activation of the planar cell polarity pathway by proteins. Cell-surface-anchored Cthrc1 bound to proteins, Frizzled proteins, and Ror2 and enhanced the interaction of proteins and Frizzled /Ror2 by forming the Cthrc1 - Frizzled /Ror2 complex. These results suggest that Cthrc1 is a Frizzled cofactor protein that selectively activates the Frizzled /PCP pathway by stabilizing ligand-receptor interaction.