Sortilin-related VPS10 domain-containing receptor 3 (SORCS3)

Sortilin-related VPS10 domain-containing receptor 3 (SORCS3) is a neuron-specific type-I transmembrane sorting receptor and a member of the VPS10p domain receptor family. Expressed at high levels in the central nervous system, especially the hippocampus and cortex, SORCS3 regulates protein trafficking by moving target proteins between the cell surface, endosomes, Golgi apparatus, and lysosomes. It directly interacts with neurotrophins such as nerve growth factor (NGF) and modulates neurotrophic signaling by facilitating receptor internalization, thus influencing synaptic transmission, plasticity, and neuronal differentiation. SORCS3 is implicated in the development and progression of multiple neuropsychiatric and neurodevelopmental disorders and functions as a tumor suppressor in glioblastoma, where its expression inversely correlates with tumor malignancy and patient prognosis. Other biological roles include attenuating BDNF signaling, regulating energy balance and neuropeptide production, and modulating long-term synaptic depression. Genetic variations in SORCS3 have been associated with risk factors for schizophrenia, bipolar disorder, depression, attention deficit-hyperactivity disorder, and autism spectrum disorder, as well as Alzheimer's disease. In summary, SORCS3 acts as a key neuronal sorting receptor essential for brain health and a potential biomarker and therapeutic target in neuropsychiatric and oncological disease contexts.

Other names

SORCS3VPS10 domain-containing receptor SorCS3VPS10 domain receptor protein SORCS 3KIAA1059Sortilin-related VPS10 domain containing receptor 3SorCS3

Not applicable, since there are no direct drugs. Known mechanisms relevant to SORCS3 include modulation of neurotrophic factor receptor internalization (NGF/p75NTR), and BDNF/TrkB signaling attenuation.