An MG53 mutant. A coiled-coil-SPRY region of the wild-type MG53 is provided with amino acids among which at least one amino acid is deleted and/or mutated to any other amino acid except serine or threonine. The prevent invention comprises a pharmaceutical composition of the MG53 mutant, a nucleic acid for coding the MG53 mutant, and the preparation method for the MG53 mutant, and uses of the MG53 mutant in the preparation of drugs for treating heart diseases, cerebrovascular diseases in diabetes mellitus, eye complications in diabetes mellitus, neuropathies in diabetes mellitus, diabetic foot diseases, kidney diseases and diseases related to cell and/or tissue damages. Particularly, the MG53 mutant can avoid or reduce metabolic side effects brought by the wild-type MG53, such as insulin resistance, obesity, diabetes mellitus, hypertension and dyslipidemia, while the heart diseases, the cerebrovascular diseases in diabetes mellitus, the eye complications in diabetes mellitus, neuropathies in diabetes mellitus, the diabetic foot diseases, the kidney diseases and the diseases related to cell and/or tissue damages are treated.
