REVIEW article
Front. Mol. Biosci.
Sec. Molecular Recognition
This article is part of the Research TopicReviews in ARF, the most misunderstood G protein I ever knew: a collection of papers exploring the multifaceted functions of an ancient protein familyView all 4 articles
Unfolding ARF and ARL GTPases: From biophysics to systems-level insights
Provisionally accepted
- 1Universite de Montreal, Montreal, Canada
- 2Institut de recherches cliniques de Montreal, Montreal, Canada
- 3Universite de Montreal Institut de Recherche en Immunologie et en Cancerologie, Montreal, Canada
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Advanced technologies to study protein biophysics, mRNA expression and protein-protein interactions at high throughput in physiological or pathological contexts are reshaping our view of the ARF family of GTPases. Most current knowledge arises from work on the classical members ARF1 and ARF6, with many ARF-like proteins (ARLs) remaining poorly characterized. Recent findings suggest that several ARLs deviate from the binary molecular switch paradigm, instead exhibiting atypical biochemical properties, highly restricted tissue-specific expression patterns, specialized subcellular localizations, and unique interaction networks. These observations raise fundamental questions about the breadth of ARF family functions, mechanisms that regulate them, and their potential impact on cellular and organismal biology. In this review, we highlight emerging insights into atypical ARF members, outline unresolved questions, and discuss how expanding our understanding beyond the classical ARF members could shed light on their unique roles in health and disease.
Keywords: ARF, ARL, GTPase, high-throughput, Biophysics, BioID, ARL14, ARL10
Received: 24 Sep 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Quirion, Strakhova, Smith and Côté. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Matthew James Smith, matthew.james.smith@umontreal.ca
Jean-François Côté, jean-francois.cote@ircm.qc.ca
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