Membrane fusion underlies such important biological processes as virus entry into host cells, intracellular protein trafficking, fertilization, formation of muscle fibres and bone resorption. In addition, pathologies such as osteoporosis and implant rejection have been attributed to aberrant fusion. Members of the tetraspanin protein superfamily have been ascribed multiple roles in membrane biology, forming extensive lateral associations and regulating the function of effector molecules by clustering them in specific areas of the membrane. The present review aims to summarize the experimental evidence for tetraspanin function in different fusion events and highlight common themes.

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