SORCS3 is a neuron-specific transmembrane receptor belonging to the VPS10p-domain receptor family that plays critical roles in protein trafficking and synaptic function. Structurally, SORCS3 contains an N-terminal VPS10p domain and exists in multiple conformations including monomeric and dimeric states 1. Its primary function involves regulating intracellular protein transport between the Golgi apparatus, endosomes, lysosomes, and plasma membrane 2, with particular importance in modulating AMPA-type glutamate receptor trafficking in the postsynaptic density to regulate synaptic transmission and plasticity 3. Genetically, SORCS3 variants are associated with multiple neuropsychiatric and neurodevelopmental disorders. Genome-wide association studies identify SORCS3 as a risk locus for attention-deficit hyperactivity disorder (ADHD), with both common and rare protein-truncating variants implicated 4. Multiple independent SNPs at SORCS3 associate with schizophrenia, bipolar disorder, and cognitive traits, with disease-protective alleles correlating with increased SORCS3 expression 3. Rare homozygous mutations cause severe neurological phenotypes including infantile spasms, intellectual disability, and developmental delay, demonstrating SORCS3's essential role in central nervous system function 2. Clinically, SORCS3 dysfunction contributes to multiple pathologies beyond neuropsychiatric disease. The receptor regulates trafficking of neurotrophin receptor p75NTR and IGF2R, suppressing glioblastoma and adrenocortical carcinoma progression 56. SORCS3 is implicated in Alzheimer's disease etiology through its roles in amyloid precursor protein trafficking and neuronal survival signaling 7.