CTNNA2 encodes αN-catenin, a cytoskeletal linker protein essential for nervous system development. It functions as a bridge between cadherin adhesion receptors and the actin cytoskeleton to regulate cell-cell adhesion 1. A key mechanism involves negative regulation of Arp2/3 complex-mediated actin polymerization; loss of αN-catenin leads to Arp2/3 de-repression and excessive actin branching that impairs neurite stability and neuronal migration 1. CTNNA2 regulates cortical neuronal migration, neurite growth, synaptic plasticity, and cerebellar-hippocampal lamination during development 1. The gene produces alternative N-terminally truncated isoforms through bidirectional transcription with intronic LRRTM1, with brain-enriched expression patterns; variants in this region associate with schizophrenia and handedness 2. Biallelic CTNNA2 mutations cause pachygyria, a severe cortical dysplasia characterized by abnormal neuronal migration 1. Additionally, CTNNA2 variants correlate with personality traits including excitement-seeking and risk-taking behaviors 3, and genetic variations associate with response to immunotherapy in small cell lung cancer 4. The gene represents the first catenin family member with documented biallelic human mutations causing developmental disease.