The expanding repertoire of ESCRT functions in cell biology and disease

James H Hurley^{1

2

3}, Alyssa N Coyne^{4

5}, Marta Miączyńska⁶, Harald Stenmark^{7

8

9}

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. jimhurley@berkeley.edu.
² California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA. jimhurley@berkeley.edu.
³ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA. jimhurley@berkeley.edu.
⁴ Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Laboratory of Cell Biology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.
⁷ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. stenmark@ulrik.uio.no.
⁸ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. stenmark@ulrik.uio.no.
⁹ Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway. stenmark@ulrik.uio.no.

PMID: 40562928
DOI: 10.1038/s41586-025-08950-y

Review

The expanding repertoire of ESCRT functions in cell biology and disease

James H Hurley et al. Nature. 2025 Jun.

. 2025 Jun;642(8069):877-888.

doi: 10.1038/s41586-025-08950-y. Epub 2025 Jun 25.

Authors

James H Hurley^{1

2

3}, Alyssa N Coyne^{4

5}, Marta Miączyńska⁶, Harald Stenmark^{7

8

9}

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. jimhurley@berkeley.edu.
² California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA. jimhurley@berkeley.edu.
³ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA. jimhurley@berkeley.edu.
⁴ Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Laboratory of Cell Biology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.
⁷ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. stenmark@ulrik.uio.no.
⁸ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. stenmark@ulrik.uio.no.
⁹ Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway. stenmark@ulrik.uio.no.

PMID: 40562928
DOI: 10.1038/s41586-025-08950-y

Abstract

The endosomal sorting complex required for transport (ESCRT) is a multicomplex machinery comprising proteins that are conserved from bacteria to humans and has diverse roles in regulating the dynamics of cellular membranes. ESCRT functions have far-reaching consequences for cell biological processes such as intracellular traffic, membrane repair, cell signalling, metabolic regulation, cell division and genome maintenance. Here we review recent insights that emphasize the pathophysiological consequences of ESCRT dysfunctions, including infections, immune disorders, cancers and neurological diseases. We highlight the possibilities of using our knowledge about ESCRT structures and functions for drug discovery.

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Conflict of interest statement

Competing interests: A.N.C. is an inventor (50%) on US patent application number 63/111,882 filed by Johns Hopkins University on methods to modulate CHMP7 expression as a therapy for neurodegeneration. A.N.C. is an inventor (90%) on US patent application number PCT/US2025/015434 filed by Johns Hopkins University on methods to modulate CHMP2B expression as a therapy for neurodegeneration. J.H.H. is a co-founder and shareholder of Casma Therapeutics, receives research funding from Hoffman-La Roche and has consulted for Corsalex. J.H.H. is an inventor on US patent application number 63/786,223 filed by the University of California, Berkeley on selective inhibitors of VPS4B and VPS4A and their use. M.M. and H.S. declare no competing interests.

References

1. Katzmann, D. J., Babst, M. & Emr, S. D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106, 145–155 (2001). - PubMed - DOI
1. Babst, M., Katzmann, D. J., Snyder, W. B., Wendland, B. & Emr, S. D. Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev. Cell 3, 283–289 (2002). - PubMed - DOI
1. Babst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T. & Emr, S. D. Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev. Cell 3, 271–282 (2002). References 1–3 identify ESCRT-I–III through genetic and biochemical analyses of Saccharomyces cerevisiae vacuolar protein sorting mutants. - PubMed - DOI
1. Hurley, J. H. & Hanson, P. I. Membrane budding and scission by the ESCRT machinery: it’s all in the neck. Nat. Rev. Mol. Cell Biol. 11, 556–566 (2010). - PubMed - PMC - DOI
1. Henne, W. M., Stenmark, H. & Emr, S. D. Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb. Perspect. Biol. 5, a016766 (2013). - PubMed - PMC - DOI

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The expanding repertoire of ESCRT functions in cell biology and disease

Affiliations

The expanding repertoire of ESCRT functions in cell biology and disease

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources