In the wisdom of Odin: modular architecture, receptor trafficking and therapeutic implications

Odin (ANKS1A) is a multidomain adaptor protein originally identified as a substrate of receptor tyrosine kinases. Over the past two decades, studies have revealed functions that extend beyond canonical growth factor signaling. At the molecular level, Odin participates in receptor signaling and membrane trafficking pathways, while at the cellular and physiological levels it contributes to processes such as ependymal cell development, ciliogenesis, and neurovascular homeostasis. Consistent with these diverse functions, alterations in Odin expression or activity have been linked to an expanding spectrum of human diseases, including cancer, neurodevelopmental disorders, neurodegeneration, ciliopathies, and cardiovascular diseases. Here, we summarize current knowledge of Odin structure and function, with particular emphasis on how its conserved modular architecture may support its role as a coordinator of receptor trafficking, signaling, and membrane homeostasis. We further discuss emerging evidence linking Odin dysfunction to human disease and review the limited therapeutic strategies currently available. Collectively, we propose a model in which Odin functions as a master regulator of receptor fate through its conserved multidomain architecture. A deeper understanding of its structural organization and molecular mechanisms may not only reveal funRdamental principles of receptor regulation but also establish Odin as a promising, yet largely unexplored, therapeutic target.

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Publication Details

Journal
Expert Opinion on Therapeutic Targets
Published
2026-09-21
DOI
https://doi.org/10.1080/14728222.2026.2738190
Primary Topic
Axon Guidance and Neuronal Signaling
Type
article
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In the wisdom of Odin: modular architecture, receptor trafficking and therapeutic implications

Stefano Gianni, Francesca Malagrinò, Valeria Pennacchietti
Expert Opinion on Therapeutic Targets
Axon Guidance and Neuronal Signaling
article

In the wisdom of Odin: modular architecture, receptor trafficking and therapeutic implications

Stefano Gianni, Francesca Malagrinò, Valeria Pennacchietti
article en

Abstract

Odin (ANKS1A) is a multidomain adaptor protein originally identified as a substrate of receptor tyrosine kinases. Over the past two decades, studies have revealed functions that extend beyond canonical growth factor signaling. At the molecular level, Odin participates in receptor signaling and membrane trafficking pathways, while at the cellular and physiological levels it contributes to processes such as ependymal cell development, ciliogenesis, and neurovascular homeostasis. Consistent with these diverse functions, alterations in Odin expression or activity have been linked to an expanding spectrum of human diseases, including cancer, neurodevelopmental disorders, neurodegeneration, ciliopathies, and cardiovascular diseases. Here, we summarize current knowledge of Odin structure and function, with particular emphasis on how its conserved modular architecture may support its role as a coordinator of receptor trafficking, signaling, and membrane homeostasis. We further discuss emerging evidence linking Odin dysfunction to human disease and review the limited therapeutic strategies currently available. Collectively, we propose a model in which Odin functions as a master regulator of receptor fate through its conserved multidomain architecture. A deeper understanding of its structural organization and molecular mechanisms may not only reveal funRdamental principles of receptor regulation but also establish Odin as a promising, yet largely unexplored, therapeutic target.

Expert Opinion on Therapeutic Targets
University of L'Aquila (IT), Sapienza University of Rome (IT)
Openalex Percentile: Top 16%
Axon Guidance and Neuronal Signaling
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In the wisdom of Odin: modular architecture, receptor trafficking and therapeutic implications — Stefano Gianni, Francesca Malagrinò, et al. · Expert Opinion on Therapeutic Targets (2026) | TGRS Research Map | TGRS