Why are CD63, CD9, CD81, as well as TSG101, HSP70, ALIX, etc., chosen as markers for exosomes or extracellular vesicles? Are these marker proteins unique to exosomes?

These protein markers were initially discovered through mass spectrometry analysis of purified extracellular vesicles as highly abundant proteins present in them. Therefore, they gradually began to be used as markers for extracellular vesicles. Actually, CD63, CD9, and CD81 are all members of the tetraspanin family. They are directly involved in the sorting of cargo into extracellular vesicles. TSG101 is a protein associated with the ESCRT complex, and ALIX is directly involved in the process of vesicle budding and scission from the membrane to form independent vesicular structures. These marker proteins are not unique to exosomes. It's primarily because they are mainly involved in the formation and secretion processes of vesicles; most are membrane proteins or ESCRT complex members and associated proteins. They originate in the cell and localize near intracellular membrane structures, so they are also present in cells. However, because the formation of extracellular vesicles depends on these molecules, and they function within vesicles, their abundance in vesicles is significantly higher than in cells.