The expanding repertoire of ESCRT functions in cell biology and disease

James H Hurley; Alyssa N Coyne; Marta Miączyńska; Harald Stenmark

doi:10.1038/s41586-025-08950-y

The expanding repertoire of ESCRT functions in cell biology and disease

Nature. 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.

Publication types

Review

MeSH terms

Animals
Disease*
Drug Discovery
Endosomal Sorting Complexes Required for Transport* / chemistry
Endosomal Sorting Complexes Required for Transport* / metabolism
Humans
Neoplasms / metabolism
Neoplasms / pathology
Nervous System Diseases / metabolism
Nervous System Diseases / pathology

Substances

Endosomal Sorting Complexes Required for Transport