Oliver's mTOR Atlas Evidence Platform
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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, …, Li H · 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.

Read the full abstract on PubMed →

At a glance

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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 type4 - Animal Study
Model systemRat cardiomyocytes (adenoviral overexpression/knockdown); mouse cardiomyocyte-specific AAV9 overexpression and knockout, transverse aortic constriction (TAC) model
JournalCirculation
Year2026
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1161/CIRCULATIONAHA.126.080371 · PMID 42770220

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Yufeng Hu first author · 1 study in the Atlas

    First author of a 2026 Circulation study identifying LAPTM4A as a novel mTORC1 activator driving pathological cardiac hypertrophy

  • Hongliang Li last author · 1 study in the Atlas

    Vice President of Gannan Medical University and Executive Director of its State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases; researcher of cardiovascular and metabolic diseases

  • Jin Zhang 1 study in the Atlas

    Builds fluorescent biosensors that show where and when signalling enzymes are active inside living cells; senior author of TORCAR, an early live-cell reporter of mTORC1

  • Xiaochun Li 1 study in the Atlas

    Solves cryo-EM structures of cholesterol-sensing membrane proteins, including the new mTORC1 regulator TM6SF1

  • Haijuan Yang 2 studies in the Atlas

    Solved, as first author in the Pavletich lab, the crystal structure of the mTOR kinase and the structure of mTORC1 activated by RHEB

More: 21 other authors

No profile yet: Li W, Hu M, Tian S, Zhou S, Liu J, Cheng X, Zhang C, Zuo Y, Liu D, Chen Y, Luo L, Bai L, Liu H, Ferdinandy P, Chiong M, Troncoso MF, Wen J, Cai J, Zhang XJ, She ZG, Zhang X

Related studies

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All 212 studies on mTORC1

Topics

Akt/PKBmTORC1

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

InterventionLAPTM4A overexpression and cardiomyocyte-specific knockout (AAV9); magnolol (LAPTM4A suppressor)
TargetmTORC1-p70S6K/4EBP1 via LAPTM4A-NEDD4L-driven K63 ubiquitination of AKT
ModelRat and mouse cardiomyocytes (TAC hypertrophy model)
EffectLAPTM4A boosts mTORC1-driven protein synthesis to promote pathological cardiac hypertrophy; cardiomyocyte LAPTM4A deletion attenuates TAC-induced hypertrophy/fibrosis.

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}
}
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