Synapsins are a family of ten homologous neuronal phosphoproteins evolutionarily conserved in invertebrate and vertebrate organisms. Synapsins appear to be crucial determinants for the fine-tuning of synaptic transmission and for synaptic remodeling. This is particularly evident in several paradigms of short-term plasticity (STP), which are specifically affected by mutations or malfunctioning of synapsin proteins. Notably, knockout of synapsin-2 in mice causes fully generalized forebrain seizures from the age of 2 months¹.

All synapsins, including synapsin-2, are composed of a highly homologous N-terminal region, and a more variable C-terminus. The N-terminal homologous region can be divided in three domains, namely domain A, B and C, which, except for domain B, are highly conserved across isoforms and species. Domain A is contains the phosphorylation site for PKA and CaMKI. Domain B, rich in small amino acids, is considered as a linker region connecting domain A to domain C. Domain C is a large region of about 300 amino acids, containing both hydrophobic and highly charged sequences with the potential to assume α-helix and β-sheet conformations. It shows extensive homology amongst the various members of the family, and mediates the core functions of synapsins¹.