Cardiomyocyte membranes (Sarcolemma and sarcoplasmic reticulum) are essential for maintaining proper excitation-contraction (E-C) coupling but are profoundly altered in diabetic cardiomyopathy, thus leading to impaired calcium signaling which detrimentally steers the heart into hypertrophic cardiomyopathy and failure. Mounting evidence implicates striatin (STRN) in cardiac function owing to its interaction with regulators of the L‐type calcium channel (LCC), i.e. caveolin‐3 (Cav-3), protein phosphatase 2A, calmodulin (CaM), and the sarcolemmal membrane associated protein (SLMAP). The CaM kinase pathway is upregulated during diabetes however, the role of STRN to this effect remains unclear. We reported that STRN is expressed in cardiomyocyte and is part of the E-C coupling module. During pathological remodeling, STRN is highly expressed in the left ventricle (LV) of Spontaneously Hypertensive Rats (SHR) at the age of 4 weeks, but declines in the SHR LV at 18 weeks, when compared to age-matched Wistar-Kyoto (WKY) rats. Silencing the STRN gene in cultured cardiomyocytes reduced their spontaneous contraction rate (~40%) and desensitized them to isoproterenol, thus phenotypically mimicking end-stage-failure. Of interest, we found that cardiac STRN interacts with SLMAP, a novel regulator of GLUT4 receptor and glucose uptake. Protein interaction assay further revealed that cardiac STRN, CaM and Cav-3 assembly is calcium sensitive. In fact, the expression levels of STRN were inversely proportional to the magnitude of interaction of Cav-3 with the CaM/STRN complex, thus indicating a role for STRN in the CaM Kinase pathway and diabetic cardiomyopathy. Collectively, our data delineate a novel role for STRN in regulating cardiomyocyte contraction, the diabetic signaling module, and the remodeling of cardiac tissue.