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Further, knockout of GSK-3α decreases cardiomyocyte apoptosis and enhances its proliferation. However, GSK-3β KO also results in hypertrophic myopathy due to cardiomyocyte hyper-proliferation. Thus GSK-3 inhibitors are named as a double-edged sword because of their beneficial and off-target effects. This review focuses on the isoform-specific functions of GSK-3 that will help in better understanding the role of GSK-3α and GSK-3β in cardiac biology and pave the way for the development of new isoform-specific GSK-3 modulator for the trea