Flotillin-1 (FLOT1)

Flotillin-1 is a membrane-associated protein and member of the SPFH (stomatin, prohibitin, flotillin, HflK/C) superfamily, encoded by the FLOT1 gene on chromosome 6[1][2][4]. It is widely expressed in human tissues and primarily localizes to the cytoplasmic side of the plasma membrane, as well as to certain intracellular compartments including the Golgi, lysosomes, endosomes, and nuclei[1][4]. Flotillin-1 forms hetero-oligomeric complexes with flotillin-2, enhancing membrane raft stabilization and organization[3][4]. As a scaffolding protein, flotillin-1 is central to the formation and functional organization of lipid rafts—specialized membrane microdomains involved in cell signaling, receptor trafficking, and endocytosis (including clathrin-independent pathways)[1][2][4]. It facilitates the endocytosis and membrane cycling of several key transporters and receptors, such as the dopamine transporter, IGF-1 receptor, and muscarinic M3 receptor[1]. Flotillin-1 is also an established marker for exosomes and serves various roles in membrane trafficking and signal transduction[1][4]. Post-translational modifications, such as S-palmitoylation, sumoylation, and phosphorylation, regulate flotillin-1’s membrane association, subcellular localization, and function[1][2][4]. Aberrant flotillin-1 expression or modification is linked to pathological processes, including tumor development (where it can function as either oncogene or tumor suppressor context-dependently), neurodegenerative diseases like Parkinson's disease, infections, cardiovascular pathology, metabolic disorders, and more[1][4]. Although flotillin-1 is not a conventional therapeutic target (such as a receptor, ion channel, enzyme, or transporter), its implications in disease progression and as a biomarker have been increasingly recognized, particularly in oncology and neurological research[1][4]. No direct drugs targeting flotillin-1 are currently established, but its modulation impacts the efficacy or localization of several druggable targets.

Other names

flotillin 1integral membrane component of caveolaeFLOT1flotillin-1