Recent studies have shown that insulin-AKT-mTORC1 signaling contributes not only to embryonic and postnatal physiological heart growth, but also to adverse LV remodeling in pathological hypertrophy. However, the exact roles of AKTs in maintaining cardiac function in the physiological setting remain to be elucidated. To determine the physiological role of major Akt subtype, Akt1 and Akt2, in cardiomyocytes, we used MerCreMer (MCM) / loxP DNA recombination to generate mice with inducible cardiomyocyte-restricted knockdown of Akt1 and Akt2 (_MHC-MCM/Akt1flox/flox/Akt2flox/flox) (icAkt1/2-DKO). After administration of tamoxifen (TMX) (20mg/kg/day x 5days), Akt1 and Akt2 in the heart were knocked down at 3days from last injection. Echocardiographic analysis showed that fractional shortening starts decreasing at 2 weeks in icAkt1/2-DKO (23% decrease at 2 weeks and 48% decrease at 4 weeks) and mean survival length was 5.3 weeks. Though we could not detect increased TUNEL positive cardiomyocytes or decreased capirary formation in the heart of icAkt1/2-DKO through all period after injection, WGA staining showed decreased cross-sectional area of each cardiomyocyte at 2 weeks after last injection accompanied by decreased ventricular weight (20% decrease). These data suggest that AKT1/2 is required to maintain normal cardiomyocyte structure and function. Autophagy and ubiquitination are primary degradative pathways in cells, and both play an important role in the regulation of cellular homeostasis through elimination of aggregated proteins, damaged organelles, and intracellular pathogens. Next we tested the hypothesis that dysregulation of autophagy and ubiqutination might be involved in the pathogenesis of cardiac atrophy and dysfunction in icAKT1/2-DKO mouse. To our surprise, autophagic activity had dynamic change within 14days. Autophagic activity assayed by LC3II/I ratio was first decreased at 3days, and then increased at 7days. Consistently, we also found that mTORC1 phosphorylation at Ser2448 and ULK1 phosphorylation at Ser757 was elevated at 3days and then decreased at 7days, suggesting that transient activation of mTORC1-ULK1 pathway potentially inhibited autophagic flux at 3days. On the other hand, total ubiquitination was decreased at 7days, although we could not see significant change in total and phosphorylated FOXO1, which are downstream target of AKT phosphorylation. Our data suggests that AKT is required to maintain cardiac structure and function in part by regulating protein degradation pathways, autophagy and ubiquitination.