Sortilin 1 (SORT1) (SORT1)

Sortilin 1 (SORT1) is a multi-ligand type I transmembrane receptor belonging to the Vps10p domain family, primarily localized in the trans-Golgi network and on the cell surface (UniProt Q99523). It plays a critical role in protein trafficking, directing ligands such as progranulin, neurotensin, and various growth factors between the cell surface, endosomes, and lysosomes (PubMed: 21040842). In neurodegenerative diseases, particularly frontotemporal dementia (FTD) caused by GRN mutations, SORT1 acts as the primary clearance receptor for progranulin; inhibiting SORT1 is a major therapeutic strategy to elevate progranulin levels and restore neuronal health (PubMed: 20833303). Additionally, SORT1 is a significant genetic locus associated with plasma low-density lipoprotein (LDL) cholesterol levels and coronary artery disease, where it influences hepatic VLDL secretion and LDL uptake (Nature: 10.1038/nature09270). Therapeutic development includes monoclonal antibodies like latozinemab that block the sortilin-progranulin interaction and potential nucleic acid-based therapies targeting SORT1 mRNA to modulate its expression in the liver or brain.

Other names

Neurotensin receptor 3NTR3Glycoprotein 95Gp95VPS10 domain-containing receptor 1100 kDa NT receptor

Inhibition of Sortilin-mediated degradation of Progranulin to increase Progranulin levels; modulation of hepatic VLDL secretion and LDL uptake.