A number of molecules have been postulated to be involved in long-term potentiation, an experimental model for learning and short-term memory. Although the molecular mechanisms of the long-term potentiation have been considerably well understood, it is not yet known why and how real memory can last very long with outstanding stability. A mechanical change of synaptic morphology at acquisition, consolidation and retention of memory is hypothesized to explain long-lasting memory. Changes in the synaptic morphology may be due, at least in part, to local extracellular proteolysis of cell adhesion and extracellular matrix molecules. Some extracellular serine proteases of the Clan PA family may modulate synaptic adhesion and associate with long-term potentiation and learning behavior. In the present review, candidate proteases that are involved in the hippocampal memory are overviewed.