Flotillin

Flotillin proteins, mainly flotillin-1 and flotillin-2, are conserved membrane-associated scaffolds that organize cholesterol- and sphingolipid-enriched lipid raft microdomains for signal transduction, endocytosis, protein trafficking, and gene-expression-linked cellular regulation^[1]. Mechanistically, flotillins bind the cytosolic leaflet of plasma membranes and endomembranes, undergo hetero-oligomerization, and assemble multiprotein complexes at the membrane-cytosol interface^[1]. In membrane trafficking, flotillin complexes regulate cargo endocytosis, endosomal sorting, and recycling, and cancer studies describe an upregulated flotillin-induced trafficking pathway carrying signaling, adhesion, and extracellular matrix remodeling proteins^[2][3]. In disease models, flotillin upregulation associates with invasive carcinomas, sarcoma, poor prognosis, and metastasis formation, while flotillin-1 supports H-Ras activation, triple-negative breast cancer invasion, and tumor growth^[3][4]. In endothelial inflammation, flotillin-1 knockdown reduces poly-I:C uptake, TLR3 signaling, VCAM-1 and ICAM-1 induction, and peripheral blood mononuclear cell adhesion^[5]. Compared with related isoforms, flotillin-1 shows distinct functional specificity because CXCL12 recruits flotillin-1, but not flotillin-2, to lipid rafts during CXCR4 signaling in T cells^[6]. For experimental applications, siRNA, shRNA, RNAi, and knockout models directly test flotillin-dependent uptake, signaling, invasion, amyloid precursor protein processing, and isoform redundancy^{[4][5][6][7][8]}.- Flotillin-1-mediated endocytosis controls LRAP uptake and cementoblast gene responses^[7]. - Flotillin-1 sustains TRPV2 surface expression and enhances TRPV2 whole-cell current density^[9]. - Flotillin double-knockout mice support in vivo analysis of APP trafficking and Aβ production^[8].