Targeting the energy guardian AMPK: another avenue for treating cardiomyopathy?

5'-AMP-activated protein kinase (AMPK) is a pivotal regulator of endogenous defensive molecules in various pathological processes. The AMPK signaling regulates a variety of intracellular intermedial molecules involved in biological reactions, including glycogen metabolism, protein synthesis, and cardiac fibrosis, in response to hypertrophic stimuli. Studies have revealed that the activation of AMPK performs a protective role in cardiovascular diseases, whereas its function in cardiac hypertrophy and cardiomyopathy remains elusive and poorly understood. In view of the current evidence of AMPK, we introduce the biological information of AMPK and cardiac hypertrophy as well as some upstream activators of AMPK. Next, we discuss two important types of cardiomyopathy involving AMPK, RKAG2 cardiomyopathy, and hypertrophic cardiomyopathy. Eventually, therapeutic research, genetic screening, conflicts, obstacles, challenges, and potential directions are also highlighted in this review, aimed at providing a comprehensive understanding of AMPK for readers.