VPS37B is a core component of the endosomal sorting complex required for transport (ESCRT-I), functioning as a structural and functional hub in vesicular trafficking. As part of the ESCRT-I complex alongside TSG101 and VPS28, VPS37B mediates the sorting of ubiquitinated cargo into multivesicular bodies for degradation 1. The complex forms helical filaments essential for membrane scission events, with VPS37B directly contributing to the scaffolding architecture that enables HIV-1 budding, autophagosome closure, and cytokinesis 2. VPS37B also regulates endocytic internalization of pattern recognition receptors like the mannose receptor following antigen presentation 3, linking it to immune tolerance mechanisms. Disease relevance spans multiple systems. VPS37B expression is significantly reduced in advanced colorectal cancer, where its depletion triggers p21-mediated cell cycle arrest and NF-κB-driven inflammatory responses, indicating a tumor suppressive role 4. In schizophrenia, VPS37B was identified as a prioritized risk gene in cross-ancestry brain eQTL analysis 5. Additionally, VPS37B is upregulated in allergic rhinitis-derived dendritic cells; targeted disruption reduces Th2 cytokine responses and alleviates allergic symptoms in murine models 3. VPS37B also appears relevant to blood pressure regulation as a candidate gene identified in vascular tissue cis-regulatory element analysis 6, and shows enriched expression in extracellular vesicle-biogenesis pathways in regenerative gingival tissue 7.