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The proline-rich transmembrane protein 2 (PRRT2) is a synaptic protein highly expressed in the central nervous system. It comprises an N-terminal proline-rich extracellular domain and two C-terminal transmembrane domains, which are highly conserved and play a pivotal role in the proteins’ function (Figure 1) [1,2]. At the cellular level, PRRT2 is mainly detected in presynaptic terminals of glutamatergic neurons in the cerebral cortex, basal ganglia, and cerebellum. The protein is involved in Ca2+-mediated neurotransmitter release through the interaction with 25 kDa Synaptosomal-Associated Protein (SNAP-25) and with other synaptic proteins such as the Vesicle Associated Membrane Protein 2 (VAMP2) and the synaptotagmins Syt1 and 2.