CTTNBP2 (cortactin-binding protein 2) is a neuron-specific regulator of dendritic spine morphology and synaptic function. Structurally, CTTNBP2 exists primarily as a short splice variant in the brain and localizes stably to dendritic spines 1. Functionally, CTTNBP2 regulates dendritic spinogenesis through two complementary mechanisms: it modulates cortactin mobility at spines by immobilizing this actin-regulating protein 1, and it scaffolds the striatin-interacting phosphatase and kinase (STRIPAK) complex to dendritic spines, specifically organizing the synaptic distribution of striatin and PP2A regulatory subunits 2. Additionally, CTTNBP2 associates with microtubules to promote their bundling and stabilization, influencing dendritic arborization 3. CTTNBP2 knockdown reduces dendritic spine density and size while decreasing synaptic transmission frequency, indicating functional impairment 1. Disease relevance includes autism spectrum disorder, where CTTNBP2 mutations have been identified 2. Recent evidence suggests CTTNBP2 acts as a tumor suppressor in neuroblastoma, with non-coding variants reducing its expression 4. Genome-wide association studies identified CTTNBP2 variants associated with structural brain connectivity, implicating cytoskeletal organization in neuropsychiatric and cognitive function 5.