Novel mTORC1 Booster LAPTM4A Potentiates Pathological Cardiac Hypertrophy.

LAPTM4A enhances mTORC1 signaling, promoting pathological cardiac hypertrophy in mice and humans, with deletion reducing hypertrophy and fibrosis.

• Why it matters: Understanding the regulation of mTORC1 and lysosomal proteins in cardiomyocytes is crucial for developing targeted therapies for cardiac hypertrophy, a leading cause of heart failure.
• What they did: Researchers screened lysosomal genes conserved across species, used viral vectors to manipulate LAPTM4A in cardiomyocytes, and performed RNA sequencing, proteomics, and drug screening to explore its role and regulation.
• The result: LAPTM4A directly interacts with NEDD4L to activate mTORC1, and its suppression via magnolol reduces hypertrophy, suggesting targeting the LAPTM4A-mTORC1 axis offers a promising therapeutic strategy.