The expression of the language-associated gene sushi repeat-containing X-linked 2 (SRPX2) is repressed by the transcription factor FOXP2. Here, SRPX2 knockdown led to a decrease in excitatory cortical synaptic density and impaired ultrasonic vocalizations in mouse pups. Modulating FOXP2 levels also regulated synaptic density by controlling SRPX2 expression. Thus, these data reveal that FOXP2 regulates synaptogenesis through SRPX2 and suggest that dysregulation of SRPX2 function might be linked to language disorders.