VPS37D is a component of the ESCRT-I complex, a critical regulator of vesicular trafficking and endocytic cargo sorting 1. As part of the ESCRT machinery, VPS37D functions in multivesicular body formation and the ubiquitin-dependent sorting of endocytic cargos for degradation 2. The protein also participates in membrane fission, protein transport to vacuoles, and viral budding via host ESCRT complexes 1. In disease contexts, VPS37D dysregulation has emerged as oncologically significant. Pan-cancer analysis reveals that abnormal ESCRT expression, including VPS37D, correlates with poor prognosis in breast cancer, adrenocortical carcinoma, bladder urothelial carcinoma, and cervical cancer 1. VPS37D shows particular prognostic value in breast cancer, where altered expression associates with tumor microenvironment composition and immune cell infiltration 1. Additionally, VPS37D has been identified in gastric and colorectal cancers with microsatellite instability 3, suggesting involvement in microsatellite instability-associated malignancies. In keratoconus, downregulation of VPS37D mRNA occurs alongside other ESCRT-I alterations, potentially contributing to abnormal exosome biogenesis 2. Gene disruption through chr7 has also been documented in neurodevelopmental disease 4. These findings position VPS37D as a potential biomarker for early cancer detection and prognosis assessment, while also implicating ESCRT dysregulation in non-neoplastic pathology.