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The Dixon lab has recently identified a family of atypical “secreted” kinases that constitute a novel branch within the human kinome tree. The Fam20-family of kinases appears to be responsible for the phosphorylation of extracellular proteins and proteoglycans. What defines these kinases is the presence of a signal peptide that directs these enzymes to the secretory pathway where phosphorylation of ER/Golgi resident proteins, extracellular domains of cell surface receptors, xylose residues within the glycosaminoglycan-protein linkage and secreted proteins occurs.