{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe SHANK family of postsynaptic scaffolding proteins plays a pivotal role in organizing the glutamatergic postsynaptic density, guiding dendritic spine formation and maturation, and ensuring efficient synaptic transmission. Disruption of SHANK1—as demonstrated by gene deletions and point mutations in various mouse models—leads to smaller, less mature dendritic spines, altered composition of postsynaptic proteins, and compromised synaptic strength that collectively contribute to learning and memory impairments. These findings underscore the essential role of SHANK1 in maintaining proper synaptic architecture and plasticity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its well‐established role in excitatory synapses, SHANK1 is crucial for maintaining the balance between excitation and inhibition within neural circuits. Alterations in SHANK1 expression affect parvalbumin‐positive (PV+) interneurons and disrupt signaling processes that underlie social communication and cognitive performance. Mouse models harboring SHANK1 mutations display notable deficits in social interactions, communication (including ultrasonic vocalizations and scent marking), and increased repetitive behaviors—phenotypes that closely mirror core symptoms of autism spectrum disorder. These data suggest that SHANK1 dysfunction contributes to imbalances in synaptic signaling and network activity critical for proper behavioral expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular and developmental levels, precise regulation of SHANK1 is essential for coordinating intracellular signaling pathways such as mGluR1–IP3R1–calcium cascades, which are activated during learning-induced synaptic remodeling. Moreover, developmental studies reveal that SHANK1 expression is dynamically regulated—not only in neurons but also in glial cells—hinting at broader roles in brain maturation and function. Alterations in SHANK1 levels or function can lead to compensatory changes in other synaptic proteins and receptor subunits, emphasizing its potential as a therapeutic target in neurodevelopmental disorders. Collectively, these insights highlight the central role of SHANK1 in preserving synaptic integrity and cognitive function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Albert Y Hung, Kensuke Futai, Carlo Sala, et al. 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