Sortilin-related receptor 1 (SORL1) (SORL1)

Sortilin-related receptor 1 (SORL1), also known as SORLA or LR11, is a large multi-domain transmembrane receptor that belongs to the Vps10p domain and LDL receptor families. It plays a critical role in the central nervous system as a neuronal sorting receptor, primarily regulating the intracellular trafficking and endosomal recycling of the amyloid precursor protein (APP). By directing APP away from amyloidogenic processing pathways in the endosomes and toward the trans-Golgi network, SORL1 effectively reduces the production of neurotoxic amyloid-beta (Aβ) peptides. Genetic variants and loss-of-function mutations in the SORL1 gene are strongly associated with both early-onset and late-onset Alzheimer's disease, making it a major therapeutic target for neurodegeneration. Beyond Alzheimer's, SORL1 is involved in lipid metabolism, neurotrophin signaling (e.g., BDNF, GDNF), and has been implicated in atherosclerosis and obesity. Current therapeutic strategies focus on restoring SORL1 expression or function through gene therapy, small molecule chaperones, or retromer-stabilizing agents to mitigate amyloid pathology and neurodegeneration.

Other names

SORLALR11LRP9SorLA-1gp250Sortilin-related receptorSorting protein-related receptor containing LDLR class A repeats

Restoration of endosomal recycling of APP; Reduction of amyloid-beta production; Promotion of Aβ clearance; Regulation of neurotrophin receptor trafficking