Synapse formation and maturation require multiple interactions between presynaptic and postsynaptic neurons. These interactions are mediated by a diverse set of synaptogenic proteins (Kegel et al. 2013, Siddiqui & Craig 2011). Initial synapse formation needs both the binding of secreted proteins to presynaptic and postsynaptic receptors, and the direct binding between presynaptic and postsynaptic transmembrane proteins. One class of molecules that plays an important role in cellular interactions in nervous system development and function is the leucine-rich glioma inactivated (LGI) protein family. These are secreted synaptogenic proteins consisting of an LRR (leucine-rich repeat) domain and a epilepsy-associated or EPTP (epitempin) domain (Gu et al. 2002). Both protein domains are generally involved in protein-protein interactions. Genetic and biochemical evidence suggests that the mechanism of action of LGI proteins involves binding to a subset of cell surface receptors belonging to the ADAM (a disintegrin and metalloproteinase) family, i.e. ADAM11, ADAM22 and ADAM23. These interactions play crucial role in the development and function of the vertebrate nervous system mainly mediating synaptic transmission and myelination (Kegel et al. 2013, Novak 2004, Seals & Courtneidge 2003).