There are many processes and signals in cells that must be turned on and off, sometimes very quickly.  How is this done? One important way is via post-translational modification of proteins such as phosphorylation or dephosphorylation. In her first talk, Dr. Anne Bertolotti introduces us to protein phosphatases, the enzymes that remove phosphate from proteins and work in opposition to protein kinases. She gives a brief history of the early experiments that showed that phosphatases are vital to regulating the stability, localization and interactions of many proteins. Bertolotti also describes more recent work demonstrating that protein phosphatases are split enzymes with a catalytic subunit and a subunit that determines substrate specificity. This selective subunit makes phosphatases exquisitely specific and attractive targets for drug development.