| SORT1 (Sortilin 1) | |
|---|---|
| Gene | [SORT1](/genes/sort1) |
| UniProt | Q99549 |
| PDB | 4J0X |
| Molecular Weight | 110 kDa |
| Subcellular Localization | Plasma membrane, Golgi apparatus, endosomes |
| Protein Family | Vps10p-domain receptor family |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers), [Cardiovascular Disease](/diseases/cvd) |
SORT1 (Sortilin 1) is a member of the Vps10p-domain receptor family that functions as a pivotal sorting receptor for various ligands, including ApoE, lipoprotein lipase, and neurotensin[1][2]. In the brain, SORT1 plays critical roles in lipid metabolism, protein trafficking, and has been genetically implicated in Alzheimer's disease risk through genome-wide association studies.
SORT1 is a type I transmembrane protein with a complex multi-domain architecture[3]:
SORT1 functions as a master sorting receptor in the secretory and endocytic pathways[1:1][4]:
In the central nervous system, SORT1 has several critical roles[5]:
GWAS have identified SORT1 variants associated with AD risk[6][7]:
SORT1 contributes to AD through multiple interconnected mechanisms[8]:
SORT1 represents a promising therapeutic target[9]:
Rogaeva, E. et al. SORT1 variants and Alzheimer's disease risk. Nature Genetics. 2007. ↩︎ ↩︎
Carlo, A.S. et al. Sortilin is essential for ApoE metabolism in the brain. Neuron. 2013. ↩︎
Jacquemet, G. et al. The Vps10p-domain receptor family. Trends in Cell Biology. 2015. ↩︎
Willnow, T.E. et al. Sortilin and lipid metabolism. Trends in Cardiovascular Medicine. 2012. ↩︎
Lane, R.F. et al. Sortilin modulates amyloid-beta metabolism. Journal of Neuroscience. 2013. ↩︎
Leduc, V. et al. SORT1 and lipid homeostasis in AD. Neurobiology of Aging. 2015. ↩︎
Zhou, L. et al. Genetic architecture of SORT1 in AD risk. Brain. 2015. ↩︎
Malmquist, K. et al. Sortilin in neurodegenerative diseases. Journal of Alzheimer's Disease. 2016. ↩︎
Huang, T.Y. & Bohnen, S. Targeting SORT1 for AD therapy. Alzheimer's Research & Therapy. 2019. ↩︎