FLOT1 (flotillin 1) is a lipid raft scaffold protein that functions as a key regulator of membrane trafficking and vesicular biogenesis. Structurally, FLOT1 localizes to caveolar membranes and lipid raft microdomains, where it participates in caveolae-like vesicle formation and organization of adherens junctions. Mechanistically, FLOT1 mediates clathrin-independent endocytosis and exosome biogenesis through interaction with RAB31 at the SPFH domain, facilitating EGFR entry into multivesicular endosomes and intraluminal vesicle formation independent of ESCRT machinery 1. FLOT1 also promotes cellular uptake of extracellular vesicles via clathrin-independent endocytosis and macropinocytosis pathways 2, and serves as a classical marker in extracellular vesicle characterization 3. In disease contexts, FLOT1 demonstrates pleiotropic roles: it enhances glioblastoma radioresistance by facilitating autophagosome-lysosome fusion through SDC1-TGM2-FLOT1-BHMT complex assembly 4, regulates epithelial-mesenchymal transition in esophageal carcinoma via FadAL-mediated Wnt3A palmitoylation 5, and associates with host susceptibility to Mycobacterium tuberculosis infection 6. FLOT1 expression dysregulation contributes to neurological diseases including Alzheimer's and Parkinson's disease, and associates with epigenetic age acceleration and human longevity 78. These findings position FLOT1 as a druggable target for cancer, neurological, and infectious disease therapeutics.