ASTN2 in ASD and neurodevelopmental disorders

This chapter reviews the role of Astrotactin 2 (ASTN2) in cerebellar development and its implications for neurodevelopmental disorders, particularly autism spectrum disorder (ASD). ASTN2 is identified as a critical gene influencing the function of the cerebellum, a brain region traditionally associated with motor control but now recognized for its roles in social cognition and emotional processing. ASTN2 mutations, including deletions and copy number variations, have been linked to increased risks of ASD and other psychiatric conditions. Studies highlight ASTN2's involvement in neuronal migration, synaptic modulation, protein trafficking, and behavior, as evidenced by mouse models displaying ASD-like behaviors when ASTN2 expression is perturbed. Additionally, ASTN2 affects the structure and function of the sole output neuron of the cerebellum, the Purkinje cell, including changes in spine density and synaptic transmission. To bridge the knowledge gap regarding the role of ASTN2 in human neurodevelopmental disorders, human induced pluripotent stem cells are being employed to further investigate ASTN2's function in human neuronal development and physiology. These studies position ASTN2 as a potential target for future therapeutic interventions in ASD and other neurodevelopmental disorders.