CNTN4 (contactin 4) is a synaptic adhesion protein that plays crucial roles in nervous system development and synaptic function. CNTN4 promotes dendrite growth and dendritic spine formation, with disruption leading to decreased excitatory synapse numbers and reduced neural activity 1. The protein regulates dendritic spine density through a mechanism dependent on its fibronectin type III (FnIII) domains 1. CNTN4 interacts with amyloid precursor protein (APP) to control neural elongation and contributes to cortical development, with Cntn4-deficient mice showing reduced motor cortex thickness 2. Beyond its neurodevelopmental functions, CNTN4 has clinical significance across multiple domains. Autism-related variants of CNTN4 lack the ability to regulate spine density and neural activity, suggesting involvement in autism spectrum disorder pathogenesis 1. The gene shows associations with antipsychotic treatment response in schizophrenia patients 3 and with thromboxane A2 formation linked to cardiovascular events 4. Additionally, CNTN4 functions as an immune checkpoint molecule, suppressing antitumor T cell responses through APP binding, making it a potential target for cancer immunotherapy 5. Copy number variants affecting CNTN4 are frequently identified in patients with neurodevelopmental disorders 6.