Transcription factor TFEB antagonizes cardiac hypertrophy and failure by enhancing lysosomal capacity and mitochondrial function

Pathological cardiac remodeling and increased afterload-driven demand contribute to heart failure. TFEB is a key regulator of lysosomal genes and mitochondrial function and is activated in response to external stress. To elucidate TFEB-dependent transcriptional programs under hypertrophic stress, we profiled left ventricular transcriptomes from a cardiomyocyte-specific TFEB knockout mouse model subjected to transverse aortic constriction (TAC) or sham surgery, with wild-type littermate controls, followed by downstream multi-omics integration.