A. Numerous transmembrane and GPI-anchored proteins undergo proteolytic processing, resulting in the release of a soluble extracellular fragment in a process called ES. B-D. ES at the synapse can be mediated by MMPs (B), ADAM10 (C) and BACE1, ADAM17, MT3-MMP and MT5-MMP (D). Cleaved proteins are indicated next to their main protease; however, each substrate can be cleaved by multiple proteases. Of note, for several proteins it is still unclear whether they are found only in one side of the synapse or both.