GSK-3 is a Ser/Thr kinase first identified as an inactivator of Glycogen Synthase. GSK-3 acts as a multifunctional downstream switch that determines the output of numerous signaling pathways. There are two mammalian GSK-3 isoforms encoded by distinct genes, GSK-3 alpha and GSK-3 beta, which are structurally similar, but functionally non-identical. GSK-3a is inhibited by phosphorylation at S21 by Akt and other kinases. GSK-3 alpha and GSK-3 beta share 85% amino acid identity. Dysregulated GSK-3 has been implicated in several diseases including type II diabetes, Alzheimers disease, bipolar disorder, and cancer.