Flotillin1

Flotillin-1, also known as FLOT1, is a ubiquitously expressed membrane-associated protein encoded by the human FLOT1 gene. It belongs to the flotillin family of SPFH (Stomatin, Prohibitin, Flotillin, HflK/C) domain–containing proteins and is conserved across eukaryotes. In cells, flotillin-1 forms hetero-oligomeric complexes with flotillin-2 (FLOT2) and together they partition into lipid raft microdomains within the plasma membrane and endosomal compartments.

Structure and localization are defined by an SPFH/band-7–related architecture that includes a membrane-associated region and a C-terminal flotillin domain. Post-translational lipidation, including N-terminal modifications, contributes to targeting flotillin-1 to cholesterol-rich raft domains. The protein localizes to the plasma membrane and endosomal membranes, where it can participate in raft-associated processes.

Functions of flotillin-1 are linked to clathrin-independent endocytosis and the trafficking and sorting of membrane proteins. Through interactions with flotillin-2 and various signaling molecules, it participates in signal transduction and may influence pathways involved in cell growth and differentiation. Flotillin-1 is also implicated in actin cytoskeleton remodeling and in the organization of membrane microdomains that modulate receptor dynamics.

Biological significance and clinical relevance have been explored in various contexts. Flotillin-1 expression and raft association have been linked to cancer progression and metastasis in some studies, and altered levels of FLOT1 have been investigated as potential biomarkers in certain malignancies. The protein also features in studies of neuronal biology and neurodegenerative disease models, where raft-mediated trafficking and signaling are relevant.

See also flotillin-2 for related protein interactions and raft functions.