SORL1

SORL1 encodes sortilin-related receptor 1, a type I transmembrane protein also known as SORLA or LR11. It functions as a cargo receptor in endocytic pathways, regulating trafficking of proteins like amyloid precursor protein (APP) and low-density lipoprotein receptor (LDLR). By sorting APP away from amyloid-beta (Aβ)-generating compartments, SORL1 inhibits Aβ production, a key pathological feature in Alzheimer’s disease (AD).
SORL1 is genetically linked to late-onset AD, with loss-of-function variants increasing disease risk. It interacts with signaling pathways including Wnt/β-catenin and Notch, influencing neuronal survival and synaptic plasticity. Current research focuses on targeting SORL1 to enhance its expression or activity, aiming to reduce Aβ accumulation and slow AD progression, though no specific drugs have entered clinical trials yet.