Novel mTORC1 Booster LAPTM4A Potentiates Pathological Cardiac Hypertrophy

Hu Y, Li W, Hu M, Tian S, Zhou S, Liu J, Cheng X, Zhang C, Zuo Y, Zhang J, Liu D, Hu Y · 2026 · Circulation · Atlas ID HU2026

What this study shows

Identifies LAPTM4A, a lysosomal transmembrane protein, as a novel booster of mTORC1 signaling in cardiomyocytes: LAPTM4A binds NEDD4L, driving K63-linked ubiquitination of AKT and downstream mTORC1-p70S6K/4EBP1-mediated protein synthesis, without affecting lysosomal autophagy. Cardiomyocyte-specific LAPTM4A deletion attenuated TAC-induced hypertrophy/fibrosis in mice; an FDA-approved-drug screen identified magnolol as a LAPTM4A suppressor with cardioprotective effect in vivo.

Abstract

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Excessive unnecessary protein accumulation in cardiomyocyte is a leading contributor for pathological cardiac hypertrophy and has been found closely regulated by the mTORC1 (mechanistic target of rapamycin complex 1) signaling and lysosome transmembrane proteins. However, the precise regulatory mechanism stratifying mTORC1 signaling and the specific functions of lysosomal proteins in protein homeostasis of cardiomyocytes remain largely unidentified. We screened lysosomal genes conserved in mice, rats, and humans.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Rat cardiomyocytes (adenoviral overexpression/knockdown); mouse cardiomyocyte-specific AAV9 overexpression and knockout, transverse aortic constriction (TAC) model); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Rat cardiomyocytes (adenoviral overexpression/knockdown); mouse cardiomyocyte-specific AAV9 overexpression and knockout, transverse aortic constriction (TAC) model
Journal	Circulation
Year	2026
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1161/CIRCULATIONAHA.126.080371 · PMID 42770220

Cite this paper

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Hu, Y., Li, W., Hu, M., Tian, S., Zhou, S., Liu, J., Cheng, X., Zhang, C., Zuo, Y., Zhang, J., Liu, D., Hu, Y., Chen, Y., Li, X., Luo, L., Yang, H., Bai, L., Liu, H., Ferdinandy, P., Chiong, M., Troncoso, M. F., Wen, J., Cai, J., Zhang, X. J., She, Z. G., Zhang, X., & Li, H. (2026). Novel mTORC1 Booster LAPTM4A Potentiates Pathological Cardiac Hypertrophy. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.126.080371

@article{HU2026,
  author       = {Hu, Y. and Li, W. and Hu, M. and Tian, S. and Zhou, S. and Liu, J. and Cheng, X. and Zhang, C. and Zuo, Y. and Zhang, J. and Liu, D. and Hu, Y. and Chen, Y. and Li, X. and Luo, L. and Yang, H. and Bai, L. and Liu, H. and Ferdinandy, P. and Chiong, M. and Troncoso, M. F. and Wen, J. and Cai, J. and Zhang, X. J. and She, Z. G. and Zhang, X. and Li, H.},
  title        = {{Novel mTORC1 Booster LAPTM4A Potentiates Pathological Cardiac Hypertrophy}},
  journal      = {Circulation},
  year         = {2026},
  doi          = {10.1161/CIRCULATIONAHA.126.080371},
  note         = {PMID: 42770220},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record HU2026) [Data set]. https://mtor-atlas.org/study/HU2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_HU2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record HU2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/HU2026/},
  doi          = {10.5281/zenodo.22059963}
}