Neurexins and neuroligins are synaptic cell-adhesion molecules that connect pre- and postsynaptic neurons, mediating trans-synaptic signaling and shaping neural network properties. Mutations in these genes are implicated in autism and other cognitive disorders, linking synaptic function to cognition. These molecules are essential for synaptic function, not formation, and their dysfunction disrupts neural networks without completely abolishing synaptic transmission. Neurexins (Nrxns) and neuroligins (Nlgns) form a trans-synaptic complex that interacts with PDZ-domain proteins, playing a central role in synaptic transmission and neural circuit function. Nrxns are type 1-membrane proteins with multiple isoforms, while Nlgns are type-I membrane proteins with simpler domain structures. Nrxns and Nlgns bind to each other and to intracellular proteins, influencing synaptic strength and plasticity. Mutations in Nrxn and Nlgn genes are associated with autism spectrum disorders (ASDs), schizophrenia, and other cognitive diseases. Studies in mice show that Nlgn and α-Nrxn knockout mice exhibit severe synaptic transmission impairments, highlighting their role in synaptic function. The complex interplay between Nrxns and Nlgns suggests they are critical for synaptic maturation and circuit-specific properties. Mutations in these genes can lead to diverse phenotypes, indicating their involvement in various cognitive disorders. The discovery of these molecules has opened new avenues for understanding synaptic function and cognitive diseases, with potential implications for diagnosis and treatment strategies.Neurexins and neuroligins are synaptic cell-adhesion molecules that connect pre- and postsynaptic neurons, mediating trans-synaptic signaling and shaping neural network properties. Mutations in these genes are implicated in autism and other cognitive disorders, linking synaptic function to cognition. These molecules are essential for synaptic function, not formation, and their dysfunction disrupts neural networks without completely abolishing synaptic transmission. Neurexins (Nrxns) and neuroligins (Nlgns) form a trans-synaptic complex that interacts with PDZ-domain proteins, playing a central role in synaptic transmission and neural circuit function. Nrxns are type 1-membrane proteins with multiple isoforms, while Nlgns are type-I membrane proteins with simpler domain structures. Nrxns and Nlgns bind to each other and to intracellular proteins, influencing synaptic strength and plasticity. Mutations in Nrxn and Nlgn genes are associated with autism spectrum disorders (ASDs), schizophrenia, and other cognitive diseases. Studies in mice show that Nlgn and α-Nrxn knockout mice exhibit severe synaptic transmission impairments, highlighting their role in synaptic function. The complex interplay between Nrxns and Nlgns suggests they are critical for synaptic maturation and circuit-specific properties. Mutations in these genes can lead to diverse phenotypes, indicating their involvement in various cognitive disorders. The discovery of these molecules has opened new avenues for understanding synaptic function and cognitive diseases, with potential implications for diagnosis and treatment strategies.