Mammalian GSK-3 exists as two isozymes, α and β, encoded by two different genes. We found that unlike other vertebrates, the GSK-3α gene is missing in birds. The α and β isozymes split from a common precursor approximately at the time of emergence of vertebrates. Although both GSK-3α and β genes are present and highly conserved in fish, amphibians, reptiles and mammals, the GSK-3α gene is missing from the genomes and transcriptomes of avian species indicating that the GSK-3α gene was lost after the split of ancestral birds from reptilians. Additionally we found that unlike other substrates of GSK-3, lack of GSK-3α resulted in a robust reduction in tau phosphorylation in the adult bird brain.