CSMD2 (CUB and Sushi Multiple Domains 2) is a synaptic transmembrane protein located on chromosome 1.1-34.3 that plays critical roles in neuronal development and synaptic function. The gene encodes a protein with complement control-related domains and is predominantly expressed during early brain development, with highest expression in inhibitory neurons 1. Mechanism: CSMD2 participates in synaptogenesis, dendritic growth, and synaptic maturation 1. The protein functions in complement regulation, influencing synaptic pruning and synaptic plasticity, processes fundamental to cognitive function and neuronal circuit refinement 23. Disease Relevance: Genetic variants in CSMD2 are associated with multiple neuropsychiatric and developmental conditions. The gene shows strong association with focal epilepsy and focal cortical dysplasia (FCD), with CSMD2 variants identified in six focal epilepsy cases, predominantly as missense variants with low allele frequencies 1. Rare variants have been identified in autism spectrum disorder patients, including both homozygous and de novo mutations 4. CSMD2 variants also associate with schizophrenia through genome-wide association studies and with severe diabetic retinopathy in type 1 diabetes 25. Additionally, CSMD2 association with Kawasaki disease treatment response suggests broader immunological functions 6. Clinical Significance: The development-dependent expression pattern and neuron-specificity of CSMD2 explain its particular relevance to focal epilepsy phenotypes, offering insights into neurodevelopmental disease mechanisms and potential therapeutic targets.