TGFß and Wnt signalling during development and human disease

A handful of previously mysterious proteins, the FAM83 family, have been found to act as master switches for a set of enzymes called CK1 kinases, which control everything from cell division to the body’s internal clock. These two systems—the TGFβ and Wnt signalling pathways—are fundamental communication networks inside cells. When they malfunction, the result can be skin and bone disorders, fibrosis, or cancer. Until now, researchers knew that CK1 kinases were central to these pathways, but they did not understand how the kinases themselves were being directed to perform so many different jobs. The FAM83 proteins appear to be the missing link, telling each CK1 kinase where to go in the cell and which specific task to carry out. This is fundamental science. The immediate output will be a molecular wiring diagram: a precise map of how FAM83 proteins control CK1 activity, location, and target selection. If that map is accurate, it will reveal new points of vulnerability in diseased cells. Drug developers could then design molecules that block a specific FAM83–CK1 interaction without disrupting the other essential jobs the kinases perform. In the long term, that could lead to more targeted treatments for cancers and fibrotic diseases, with fewer side effects than current therapies that hit the entire pathway.