The gene-silencing complex HUSH might be involved in complex disorders affecting the brain and neurons. However, its mechanism of action remains unclear. Researchers now uncover the in vivo targets and physiological functions of a component of the HUSH gene-silencing complex and one of its associated proteins. The work, conducted in laboratory mouse models and human brain organoids, links the HUSH complex to normal brain development, neuronal individuality and connectivity, as well as mouse behavior.