Extracellular vimentin: Battle between the devil and the angel

Vimentin, an intracellular cytoskeletal protein, can be secreted by various cells in response to conditions such as injury, stress, senescence, and cancer. Once vimentin is secreted outside of the cell, it is called extracellular vimentin. This extracellular vimentin is significantly involved in pathological conditions, particularly in the areas of viral infection, cancer, immune response, and wound healing. The effects of extracellular vimentin can be either positive or negative, for example it can enhance axonal repair but also mediates SARS-CoV-2 infection. In this review, we categorize the functional implications of extracellular vimentin based on its localization outside the cell. Specifically, we classify extracellular vimentin into two distinct forms: surface vimentin, which remains bound to the cell surface, and secreted vimentin, which refers to the free form that is completely released outside the cell. Overall, extracellular vimentin has a dual nature that encompasses both beneficial and detrimental effects on the functionality of cells, organs and whole organisms. Here, we summarize its effects in viral infection, cancer, immune response and wound healing. We find that surface vimentin is often associated with negative consequences, whereas secreted vimentin manifests predominantly with positive influences. We found that the observed effects of extracellular vimentin strongly depend on the specific circumstances under which its expression occurs in cells.