Plain-language summary
Large extracellular vesicles (lEVs) are a broad family of membrane-bound particles larger than 200 nm, and this review argues that they deserve to be studied as distinct entities rather than treated as background debris. Unlike small extracellular vesicles, which can arise from the endosomal system, most lEVs form directly at the plasma membrane, yet the individual subtypes follow clearly different assembly routes. The authors map the current catalogue: the long-recognised apoptotic bodies, microvesicles and large oncosomes, alongside family members described only recently, such as migrasomes, exophers, mitophers, blebbisomes and large ageing neutrophil-derived vesicles. They then compare what is known about how each subtype is generated, which cargo it carries, and which physiological and pathological processes it takes part in. A recurring problem, the review notes, is that these populations overlap in size and surface markers, which makes clean separation difficult. Emerging tools for multidimensional characterisation, loss-of-function studies and mechanistic analysis are singled out as the most promising way forward, provided they are integrated carefully enough for the field to reach rigorous, reproducible results.
Key findings
- Large extracellular vesicles (lEVs) are a heterogeneous group of membrane-bound particles larger than 200 nm, distinct from the smaller endosome-derived vesicles.
- Most lEVs bud directly from the plasma membrane, but each subtype follows its own biogenesis route and carries a characteristic cargo.
- The classical family of apoptotic bodies, microvesicles and large oncosomes has been extended by newer subtypes such as migrasomes, exophers, mitophers, blebbisomes and large ageing neutrophil-derived vesicles.
- Because lEV subtypes overlap in size and surface markers, the authors call for integrated multidimensional characterisation, loss-of-function and mechanistic studies to keep results rigorous and reproducible.
Original abstract
Large extracellular vesicles (lEVs) are heterogeneous structures with sizes that exceed 200 nm. Unlike small extracellular vesicles, which originate from either the endosomal system or the plasma membrane, most lEVs stem directly from the plasma membrane, although the various lEV subtypes have distinct biogenesis pathways. Emerging findings have helped to update lEV classification and have provided insights into lEV biogenesis, cargo, physiological functions and relevance in disease. Classical lEVs include apoptotic bodies, microvesicles and large oncosomes, whereas detached migrasomes, exophers, mitophers, blebbisomes, large ageing neutrophil-derived vesicles were only identified later. The study of these diverse lEV subtypes has been challenging, but emerging technologies, including tools that enable multidimensional characterization, loss-of-function studies and mechanistic analyses, are likely to advance the field further, especially if they are appropriately integrated to ensure rigour and reproducibility.
Frequently asked questions
What did this study find?
Large extracellular vesicles (lEVs) are a broad family of membrane-bound particles larger than 200 nm, and this review argues that they deserve to be studied as distinct entities rather than treated as background debris. Unlike small extracellular vesicles, which can arise from the endosomal system, most lEVs form directly at the plasma membrane, yet the individual subtypes follow clearly different assembly routes. The authors map the current catalogue: the long-recognised apoptotic bodies, microvesicles and large oncosomes, alongside family members described only recently, such as migrasomes, exophers, mitophers, blebbisomes and large ageing neutrophil-derived vesicles. They then compare what is known about how each subtype is generated, which cargo it carries, and which physiological and pathological processes it takes part in. A recurring problem, the review notes, is that these populations overlap in size and surface markers, which makes clean separation difficult. Emerging tools for multidimensional characterisation, loss-of-function studies and mechanistic analysis are singled out as the most promising way forward, provided they are integrated carefully enough for the field to reach rigorous, reproducible results.
Was this tested in humans or in the laboratory?
This is a review: it summarises and weighs up previously published studies rather than presenting new experiments.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1038/s41580-026-01021-8
How to cite this paper
Huang Yuwei, Xie Renxiang, Ma Junjie, Yu Li. Towards a systematic understanding of the diverse subtypes, biogenesis and functions of large extracellular vesicles.. Nature reviews. Molecular cell biology. 2026, 2026-10-05. DOI: 10.1038/s41580-026-01021-8
Source & verification
- Journal: Nature reviews. Molecular cell biology
- Published: 5 October 2026
- DOI: 10.1038/s41580-026-01021-8
- PubMed ID: 42834138
- Indexed via: pubmed
- MeSH terms: —