Neurexins (NRXNs) and neuroligins (NLGNs) are best characterized synaptic cell-adhesion molecules. They are part of excitatory glutamatergic and inhibitory GABAergic synapses in mammalian brain, mediate trans-synaptic signaling, and shape neural network properties by specifying synaptic functions. As cell-adhesion molecules, NRXNs and NLGNs probably function by binding to each other and by interacting with intracellular PDZ-domain proteins, but the precise mechanisms involved and their relation to synaptic transmission remain unclear. The binding of NRXNs and NLGNs to their partners, helps to align the pre-synaptic release machinery and post-synaptic receptors. The importance of neurexins and neuroligins for synaptic function is evident from the dramatic deficits in synaptic transmission in mice lacking Nrxns or Nlgns. In humans, alterations in NRXNs or NLGNs genes are implicated in autism and other cognitive diseases, connecting synaptic cell adhesion to cognition and its disorders (Sudhof 2008, Craig et al. 2006, Craig & Kang 2007).