In this review, we summarize the biological function of MG53 with its potential mechanisms in cardiac tissue (Fig. 1), discuss current debates regarding the role of MG53 in diabetic cardiomyopathy (Table 1), and potential clinical applications of recombinant MG53 protein in the management and treatment of heart diseases (Table 2). The gene discussed is TRIM72; the disease is diabetic cardiomyopathy.