ASTN2 (astrotactin 2) is a transmembrane neuronal protein that plays crucial roles in neurodevelopment and synaptic function. ASTN2 mediates neuronal cell adhesion and migration processes, particularly in cerebellar development where it is highly expressed 1. The protein undergoes intramembrane proteolysis in its second transmembrane domain, which appears to be important for its maturation and function 2. ASTN2 regulates cerebellar Purkinje cell synaptic activity and dendritic spine morphology, with knockout mice displaying autism spectrum disorder (ASD)-related behaviors including hyperactivity, repetitive behaviors, and impaired social interactions 1. Loss of ASTN2 function leads to alterations in mitochondrial dynamics through regulation of ZNF558 and subsequent effects on mitophagy-related gene SPATA18 3. Clinically, ASTN2 variants are associated with multiple neurodevelopmental and psychiatric conditions. Mutations have been identified in individuals with intellectual disability, ASD, and ADHD 45. Additionally, ASTN2 polymorphisms influence pain sensitivity and opioid requirements in surgical patients, suggesting broader physiological roles 6. The gene shows genetic correlations with schizophrenia risk, indicating shared pathogenic mechanisms across psychiatric disorders 7. These findings establish ASTN2 as an important regulator of neuronal function with significant clinical implications for neurodevelopmental disorders.