Astrocyte-derived hevin: A molecular bridge between synaptic maturation and neurodevelopmental disorders

Hevin (SPARCL1) is an astrocyte-secreted matricellular protein that plays a pivotal role in excitatory synapse formation by physically bridging presynaptic neurexin-1α (Nrx1α) and postsynaptic neuroligin-1B (NL1B), two synaptic adhesion molecules whose direct interaction is normally weakThrough this function, hevin regulates synaptic maturation, stability, and plasticity across development and adulthood. In this narrative review, we synthesize current molecular, cellular, and animal-based evidence to examine the role of astrocyte-derived hevin in synapse development and its relevance to neurodevelopmental disorders. Recent evidence links hevin dysregulation to the pathophysiology of multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), fragile X syndrome (FXS) and schizophrenia. In ASD, mutations and altered expression of hevin impair thalamocortical connectivity, synaptic pruning, and astrocytic regulation of excitatory synapses. In FXS, region- and age-specific changes in hevin expression correlate with disrupted excitatory–inhibitory balance. In schizophrenia, hevin dysfunction may weaken excitatory transmission via impaired Nrx1-α and NL1-B interactions and contribute to NMDA receptor hypofunction. Together, the evidence reviewed positions hevin as a critical molecular link between astrocyte–neuron communication, synaptic architecture, and the neurodevelopmental trajectories underlying diverse psychiatric conditions. Understanding hevin’s regulatory mechanisms may therefore suggest novel therapeutic strategies targeting synaptic dysfunction across neurodevelopmental disorders.