The study investigates the effects of lithium ions (Li⁺) on glycogen synthase kinase-3 (GSK-3) activity and its role in cell fate and differentiation. Li⁺ is shown to inhibit GSK-3β and Drosophila Zw3sgg, a homologue of GSK-3, at physiological doses, without affecting other protein kinases. The inhibition is reversible in vitro and in intact cells. Treatment with Li⁺ reduces GSK-3-dependent phosphorylation of the microtubule-associated protein Tau and induces the accumulation of cytoplasmic Armadillo/β-catenin, mimicking Wingless signalling. These findings suggest that Li⁺ acts as a specific inhibitor of GSK-3 and may contribute to its effects on development and differentiation. The study also discusses the potential mechanisms by which Li⁺ stabilizes β-catenin through GSK-3 inhibition and the therapeutic implications of this mechanism in bipolar disorder.The study investigates the effects of lithium ions (Li⁺) on glycogen synthase kinase-3 (GSK-3) activity and its role in cell fate and differentiation. Li⁺ is shown to inhibit GSK-3β and Drosophila Zw3sgg, a homologue of GSK-3, at physiological doses, without affecting other protein kinases. The inhibition is reversible in vitro and in intact cells. Treatment with Li⁺ reduces GSK-3-dependent phosphorylation of the microtubule-associated protein Tau and induces the accumulation of cytoplasmic Armadillo/β-catenin, mimicking Wingless signalling. These findings suggest that Li⁺ acts as a specific inhibitor of GSK-3 and may contribute to its effects on development and differentiation. The study also discusses the potential mechanisms by which Li⁺ stabilizes β-catenin through GSK-3 inhibition and the therapeutic implications of this mechanism in bipolar disorder.