CTNND2

CTNND2 encodes delta-2-catenin, a member of the catenin protein family. The protein is predominantly expressed in neurons and is associated with cadherin-based adherens junctions. It plays a role in cell adhesion and in the regulation of the cytoskeleton, contributing to neuronal development, dendritic arborization, and synapse formation.

Delta-2-catenin binds to the cytoplasmic domains of classical cadherins and links these complexes to the actin cytoskeleton. Through its interactions, it functions as a scaffolding component at synaptic junctions and influences the growth and maturation of dendrites and dendritic spines, thereby impacting synaptic structure and potentially plasticity in brain networks.

Clinical significance is emerging from genetic studies. Alterations in CTNND2, including deletions, duplications, and sequence variants, have been reported in individuals with neurodevelopmental disorders such as intellectual disability, developmental delay, autism spectrum disorders, and sometimes epilepsy. In many cases, CTNND2 changes occur within larger genomic intervals, reflecting the complexity of genetic contributions to these conditions. Animal models, including CTNND2-deficient mice, show abnormalities in neuronal morphology and learning-related behaviors, supporting a role for this gene in brain development and function.

Overall, CTNND2 is viewed as a brain-enriched gene encoding a catenin that participates in cadherin-mediated adhesion and cytoskeletal regulation, with emerging evidence linking its disruption to neurodevelopmental phenotypes. Further research aims to clarify its precise molecular pathways and contribution to human disease.