In the hearts of RagA/B cKO mice, a mouse model of LSD, YAP is stabilized in the CM nucleus, interacts with TFEB, and stimulates autophagy. Since the function of lysosomes is severely and irreversibly impaired in this model of LSD, stimulation of autophagy is detrimental. In CMs with RagA/B downregulation, suppression of autophagy is protective, whereas activation of autophagy is detrimental. Together with our recent results showing that hyperactivation of YAP promotes dedifferentiation of CMs (17), we propose that YAP promotes heart failure in LSD.