Lithium has been used to treat bipolar disorder and unipolar depression for many years and has proven to be very successful in preventing suicide (Snitow et. al, 2021). Low dose lithium has also been proposed to slow the development of dementia. Lithium inhibits the protein kinase Glycogen Synthase Kinase-3 but also inhibits metabolic enzymes such as inositol monophosphatase, phosphoglucomutase, and fructose 1,6 diphosphatase. It therefore remains unclear which target of lithium mediates the therapeutic response. The goal of this project is to use molecular modeling coupled with wet bench experiments to identify a GSK-3 mutant that is resistant to lithium and then use this mutant to test whether the biological and behavioral effects of lithium are mediated through GSK-3 inhibition.