WNTs, a family of secreted lipoglycoproteins, originally identified as mammary oncogenes, bind and activate their receptors, the Frizzleds. This review will present WNT-Frizzled interaction, Frizzled pharmacology, and signaling pathways—both basic paradigms and novel developments. The aim is to summarize the current status of our knowledge and point at apparent gaps. The involvement of Frizzleds in embryogenesis, adult physiology, and some diseases, renders these receptors a suitable target for drug development and therapy. The increasing understanding of molecular aspects of the WNT/Frizzled signaling system will support the discovery of drug targets as well as the advancement of therapeutic applications targeting FZD signal transduction. Currently, promising lines of therapy are evolving, for example, cancer therapy, treatment of cardiovascular and inflammatory diseases, and stem cell-based replacement therapy for neurodegenerative conditions such as Parkinson's disease.

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