Sortilin-related receptor 1 (SORL1)

Sortilin-related receptor 1 (SORL1, also known as SORLA or LR11) is a large multidomain type I transmembrane sorting receptor predominantly expressed in the central nervous system[1]. SORL1 mediates endosomal recycling of membrane-bound proteins, including amyloid precursor protein (APP) and glutamate receptor subunit GluA1, thus regulating their cellular trafficking and processing[1][2][3]. It plays a key role in neuronal maintenance by guiding receptors and cargo from early endosomes to other cellular compartments via interaction with the retromer complex. Mutations in SORL1 confer high risk for Alzheimer's disease—similar to APP and presenilins—making it the fourth major causal gene for AD. Pathogenic variants disrupt its function, especially those affecting dimerization or interaction with the retromer complex, resulting in impaired protein recycling and increased amyloidogenic APP processing. SORL1’s pathogenicity is relevant in both early- and late-onset forms of AD, and its deficiency is a proposed upstream trigger for sporadic Alzheimer’s disease development[1][2][3]. SORL1 is studied as a potential therapeutic target for AD, mainly through strategies that enhance retromer-mediated recycling to shift APP processing away from amyloid beta peptide generation.

Other names

SORLALR11SORLA-1LRP9gp250C11orf32LDLR relative with 11 ligand-binding repeatsmosaic protein LR11Sortilin-related receptorSorting protein-related receptor containing LDLR class A repeatsL(DLR class) A repeats containing

Enhancement of retromer function to promote non-amyloidogenic APP recycling; Stabilization of endosomal recycling to decrease amyloidogenic processing