Extracellular functions of 14-3-3 adaptor proteins

14-3-3s are a family of adaptor proteins with a wide range of roles in cell signaling. Although they are primarily localized within the cytosol, 14-3-3s are also known to be present in the extracellular environment. Externalization of 14-3-3 can occur as a result of cell death or physiologically via release in exosomes. Interesting biological activities with relevance for tissue homeostasis and disease are now being described for extracellular 14-3-3s. Moreover, aminopeptidase N (APN) has been identified as a cell surface receptor for 14-3-3s. Here we review the array of bioactivities that have been ascribed to extracellular 14-3-3s and discuss applications as biomarkers and as targets for drug development.