SHANK1 encodes a postsynaptic scaffolding protein that functions as a critical adapter in excitatory synapses, interconnecting glutamate receptors with the actin cytoskeleton and organizing dendritic spine structure 1. The protein serves as a core component of the postsynaptic density (PSD), facilitating synaptic maturation and proper neural circuit function through protein-protein interactions 2. SHANK1 operates within the Neurexin-Neuroligin-Shank pathway, which is essential for synapse formation, maturation, and maintenance 2. Functionally, SHANK1 contains a C-terminal domain that binds to Homer1, a critical linker protein, and proper synaptic localization is required for normal function 3. Clinically, de novo truncating mutations in SHANK1 are associated with autism spectrum disorders and broader neurodevelopmental disorders 43. These mutations disrupt protein-protein networks in dendritic spines and impair synaptic localization 3. Mouse models demonstrate that Shank1 knockout produces ASD-relevant behavioral phenotypes including deficits in social behavior, communication, and repetitive behaviors 5. Additionally, SHANK1 has been implicated in other conditions including Alzheimer's disease through brain iron regulation 6 and unexpectedly shows oncogenic properties in colon cancer 7, suggesting diverse cellular functions beyond synaptic scaffolding.