Sortilin 1 (SORT1)

Sortilin 1 is a type I transmembrane glycoprotein encoded by the *SORT1* gene and a member of the vacuolar protein sorting 10 protein (Vps10p) domain receptor family[1][2]. It acts as a multi-ligand sorting receptor, mediating the trafficking of proteins between the Golgi apparatus, endosomes, lysosomes, and the plasma membrane. Sortilin is broadly expressed, with high abundance in the central nervous system and roles in lipid and glucose homeostasis, neural development, and cell death. It interacts with several ligands (notably neurotensin, pro-neurotrophins) and protein partners, and is involved in pathways related to metabolic regulation and neurodegeneration. Aberrations in its function are implicated in coronary artery disease, Alzheimer’s disease, and various cancers[1][2][3][5]. At the molecular level, sortilin’s structure features a signature ten-bladed β-propeller within a VPS10 domain, facilitating diverse ligand interactions. While not yet a mainstream drug target, emerging studies highlight its value in human disease and as a candidate for therapeutic modulation.

Other names

SortilinNeurotensin receptor 3 (NTR3)VPS10 domain-containing receptorSORT1 proteinVPS10p domain receptor

Modulation of ligand binding (e.g., neurotensin, proNGF, proBDNF) and receptor trafficking. Small molecule allosteric modulation of ligand binding sites. Sortilin-derived peptides or analogs (such as spadin) can inhibit or modulate activity of interacting proteins (e.g., TREK-1 potassium channel).