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This review clarifies RhoGDI2’s contradictory roles in cancer, emphasizes its underrecognized functions in immunity, and outlines approaches to explain its complex regulation.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-dual-function-of-rhogdi2-in-immunity-and-cancer/378650/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/the-dual-function-of-rhogdi2-in-immunity-and-cancer/378650.png","ImageObject",300,407,{"name":42,"@type":43},"pixelkiddo","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is RhoGDI2 and what role does it play in Rho GTPase regulation?","Question",{"text":63,"@type":64},"RhoGDI2 is a guanine nucleotide dissociation inhibitor specific for Rho family small GTPases. It helps regulate the active GTP-bound versus inactive GDP-bound states by sequestering the GDP-bound form in the cytosol.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does the review describe RhoGDI2’s relationship to cancer and immunity?",{"text":68,"@type":64},"RhoGDI2 is implicated in multiple human cancers and in immune regulation, and it can display a dual, opposite role depending on context. The review aims to clarify these seemingly contradictory functions.",{"name":70,"@type":61,"acceptedAnswer":71},"Why does the review emphasize that RhoGDI2’s mechanisms are not fully understood?",{"text":72,"@type":64},"Despite involvement in many biological processes and accumulating evidence, the mechanistic functions of RhoGDI2 remain unclear. 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Deroanne *  \nCitation: Tripathi, M.; Colige, A.; Deroanne, C.F. The Dual Function of RhoGDI2 in Immunity and Cancer. Int. J. Mol. Sci. 2023, 24, 4015 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24044015  \nAcademic Editor: Arcangelo Liso  \nReceived: 31 January 2023  \nRevised: 10 February 2023  \nAccepted: 14 February 2023  \nPublished: 16 February 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nLaboratory of Connective Tissues Biology, GIGA-Cancer, University of Li±ge, 4000 Li±ge, Belgium  \n* Correspondence: [c.deroanne@uliege.be](c.deroanne@uliege.be)  \nAbstract: RhoGDI2 is a guanine nucleotide dissociation inhibitor (GDI) specific for the Rho family of small GTPases. It is highly expressed in hematopoietic cells but is also present in a large array of other cell types. RhoGDI2 has been implicated in multiple human cancers and immunity regulation, where it can display a dual role. Despite its involvement in various biological processes, we still do not have a clear understanding of its mechanistic functions. This review sheds a light on the dual opposite role of RhoGDI2 in cancer, highlights its underappreciated role in immunity and proposes ways to explain its intricate regulatory functions.  \nKeywords: RhoGDI2 1; RhoGDI1 2; Rho GTPases 3; cancer 4; immunity 5  \n1. Introduction  \nRho GTPases are highly conserved members of the Ras superfamily, which are best known to organize the actin and microtubule cytoskeleton thereby defining the cell shape and migration. They also control a wide variety of signaling pathways that regulate crucial biological processes such as vesicle transport, cell division and gene transcription [1–3] . Rho GTPases cycle between an active GTP-bound form and an inactive GDP-bound form. This activity is regulated by three classes of proteins: guanine nucleotide exchange factors (GEFs) catalyze the exchange of GDP for GTP to activate the GTPase; whereas GTPase-activating proteins (GAPs) increase the intrinsic GTP hydrolysis rate of the GTPase and inactivate it; and guanine nucleotide dissociation inhibitors (GDIs) sequester the GDP-bound form of GTPases in the cytosol to prevent their activation by GEFs or ubiquitin-mediated degradation (Figure 1) [4] . Aberrant signaling of Rho GTPases and their regulators is commonly found in many human cancers and has been attributed to several mechanisms [5–10] .  \nTo this date, nearly 85 RhoGEFs and 66 RhoGAPs have been identified for nearly 20 Rho GTPase family members, wherein, in stark contrast, only three human RhoGDIshave been identified so far: RhoGDI1 (or RhoGDI􀀋), RhoGDI2 (or RhoGDI􀀌 or D4-GDIor Ly-GDI) and RhoGDI3 (or RhoGDI􀀍) [8] . All three reside exclusively in the cytoplasm wherein RhoGDI1 is ubiquitously expressed [11,12] . RhoGDI2 was initially believed to be expressed specifically in hematopoietic cells [13,14] but subsequently has also been found in various other cell types and tissues, including cancer cells [8] . RhoGDI3 is primarily expressed in the brain, lung, kidney, testis and pancreas where it targets the Golgi, and shows specificity towards RhoB and RhoG [15] . There is not much known about RhoGDI3 in cancer and immunity, therefore it will not be discussed further in this review.  \nRhoGDI1 and RhoGDI2 have been implicated in multiple human cancers through their involvement in cancer cell migration, invasion and metastasis and, thus, are regarded as attractive targets for cancer biology [8] . RhoGDI2 has largely remained in RhoGDI10 s shadow because of its lower abundancy and more rest","cbCaiimRz012sDo2","https://ap.wps.com/l/cbCaiimRz012sDo2","pdf",3105601,"English","# Abstract\n# Introduction\n## Rho GTPases and regulatory proteins\n## RhoGDI family overview\n# RhoGDI1 and RhoGDI2: Similarities and Differences\n## Discovery, expression patterns, and functions","[{\"question\":\"What is RhoGDI2 and what role does it play in Rho GTPase regulation?\",\"answer\":\"RhoGDI2 is a guanine nucleotide dissociation inhibitor specific for Rho family small GTPases. It helps regulate the active GTP-bound versus inactive GDP-bound states by sequestering the GDP-bound form in the cytosol.\"},{\"question\":\"How does the review describe RhoGDI2’s relationship to cancer and immunity?\",\"answer\":\"RhoGDI2 is implicated in multiple human cancers and in immune regulation, and it can display a dual, opposite role depending on context. The review aims to clarify these seemingly contradictory functions.\"},{\"question\":\"Why does the review emphasize that RhoGDI2’s mechanisms are not fully understood?\",\"answer\":\"Despite involvement in many biological processes and accumulating evidence, the mechanistic functions of RhoGDI2 remain unclear. The article highlights the need to better explain its intricate regulatory control.\"}]","The Dual Function of RhoGDI2 in Immunity and Cancer | PDF",1790231752,48]