Disclosed in the present invention is a MG53 mutant, wherein any one or two or more of 7 cysteines in the RING domain at the N-terminal of MG53 are mutated into mutations of non-polar amino acids. The MG53 mutant has preventive / therapeutic effects and uses in the protection of the heart, and the treatment of heart diseases caused by cell death, while avoiding the side effects caused by MG53 such as insulin resistance, obesity, and diabetes, etc.
