Autism spectrum disorder (ASD) affects a significant portion of children in the United States and has traditionally been linked to neuronal abnormalities. However, recent research suggests that altered neuro-immune responses, particularly involving microglia, may also contribute to ASD. While ASD has been thought of as a polygenic disorder, studies have identified SCN2A deficiency as a prominent monogenic cause. A mouse model lacking the SCN2A gene displays behavioral and neuronal traits similar to ASD. In this study, researchers found that microglia in these mice are partially activated and excessively prune synapses, particularly during certain developmental stages. Inhibiting microglial activity partly restores synaptic function. To validate these findings in human cells, researchers developed a model using cerebral organoids with an SCN2A mutation, finding similar microglial behavior. This study underscores the importance of microglia in ASD associated with SCN2A deficiency across different species.