ANK3 encodes ankyrin-G, a neuron-enriched scaffolding protein critical for neuronal development and cellular organization 1. In neurons, ankyrin-G regulates axonal polarity and ion channel clustering at axon initial segments and nodes of Ranvier, while also functioning in oligodendrocytes to facilitate paranodal junction assembly 2. The protein may serve as part of a membrane cytoskeleton in association with beta-spectrin [UniProt]. ANK3 variants are associated with multiple neuropsychiatric and developmental disorders. Genome-wide association studies and meta-analyses consistently implicate ANK3 polymorphisms (rs10994336, rs1938526, rs10761482) in bipolar disorder susceptibility 3, with rs10994336 linked to altered facial affect processing via early event-related potentials 4. ANK3 variants also confer schizophrenia risk across populations 15, supporting shared genetic mechanisms between bipolar disorder and schizophrenia. Beyond neuropsychiatric disease, biallelic and monoallelic ANK3 variants cause syndromic intellectual disability with language delay, autism spectrum disorder, motor impairment, and epilepsy, with biallelic variants producing more severe phenotypes 6. Additionally, ANK3 variants are implicated in ocular coloboma pathogenesis during early eye development 7. These findings underscore ANK3's essential roles in nervous system development, neural connectivity, and its dysfunction in multiple neurodevelopmental and psychiatric conditions.