Sortilin-related receptor (SORL1) (SORL1)

Sortilin-related receptor (SORL1), also known as SORLA or LR11, is a large type I transmembrane protein that functions as a key regulator of endosomal protein sorting (UniProt: Q92673). It is a member of both the vacuolar protein sorting 10 protein (Vps10p) domain receptor family and the low-density lipoprotein receptor (LDLR) family (NCBI Gene: 6653). SORL1 acts as a molecular chaperone for the amyloid-beta precursor protein (APP), trafficking it from endosomes back to the trans-Golgi network, which prevents its cleavage into neurotoxic amyloid-beta (Aβ) peptides (Andersen et al., 2016). Genetic evidence strongly links SORL1 loss-of-function mutations to both sporadic and familial Alzheimer's disease, making it a primary target for neuroprotective therapies (Rogaeva et al., 2007). Beyond its role in the brain, SORL1 is involved in regulating lipid metabolism and the migration of smooth muscle cells, contributing to the pathology of atherosclerosis (PubMed: 28253444). Therapeutic development currently focuses on increasing SORL1 expression or enhancing its retromer-mediated trafficking to restore normal APP processing and reduce Aβ accumulation.

Other names

SORLALR11VPS10 domain-containing receptor SorLASortilin-related receptor L(DLR) class A antigen-like repeat-containing protein

Upregulation of SORL1 expression or stabilization of the SORL1-retromer complex to promote non-amyloidogenic APP trafficking.