EVI5 is a Rab-GTPase-activating protein that regulates cell cycle progression, cytokinesis, and intracellular membrane trafficking. It stabilizes FBXO5 and Emi1 proteins to promote cyclin-A accumulation during interphase and govern mitotic fidelity. EVI5 also functions in endosome recycling and iron trafficking via interactions with transferrin and ferritin. EVI5 has emerged as a notable oncogene across multiple cancer types. In non-small cell lung cancer, EVI5 upregulation promotes proliferation, migration, and metastasis through the miR-486-5p-EVI5-TGF-β/Smad axis 1. In laryngeal cancer, EVI5 stabilizes the c-MYC oncogene by antagonizing FBXW7-mediated ubiquitination, driving cell cycle progression and tumorigenesis 2. In hepatocellular carcinoma, EVI5 is a direct target of miR-135b, with the HSF1/miR-135b/RECK&EVI5 axis promoting invasion and metastasis 3. In lung adenocarcinoma, EVI5 regulates PD-L1 expression through Rab11 interaction, modulating the tumor immune microenvironment 4. A novel EVI5::BRAF fusion has been reported in infantile fibrosarcoma 5, and EVI5 cooperates with BCL6 in lymphomagenesis 6. Genetic studies implicate EVI5 as a high-risk locus for multiple sclerosis 7, with recent Mendelian randomization analysis identifying EVI5 as a potential therapeutic target for MS 8. Drosophila studies reveal that Evi5-depletion impairs iron homeostasis in the central nervous system, linking altered EVI5 function to iron dysregulation observed in MS 9.