SORL1 (sortilin-related receptor 1) is a critical sorting receptor that regulates endosomal trafficking in neurons and other brain cells. Its primary function involves directing intracellular trafficking of multiple proteins, most notably amyloid precursor protein (APP), by facilitating recycling from early endosomes back to the trans-Golgi network or cell surface 1. SORL1 works in conjunction with the retromer trafficking complex to prevent APP from entering late endosomes where amyloidogenic Aβ peptides are generated 2. Beyond APP, SORL1 regulates trafficking of other neurologically relevant proteins including TRKB (BDNF receptor), GLUA1 (glutamate receptor), APOE, and CLU 13. The protein is particularly important in microglia, where SORL1 deficiency leads to lysosomal dysfunction, impaired degradation of phagocytosed material including Aβ fibrils, and altered immune responses 4. Loss-of-function variants in SORL1 are causative for Alzheimer's disease, with decreased SORL1 expression consistently observed in AD brains 56. The gene represents a convergence point for AD pathology, as SORL1 deficiency leads to early endosomal swelling—a hallmark cytopathological feature of AD 1. These findings position SORL1 as both a key AD risk factor and potential therapeutic target for addressing endosomal-lysosomal dysfunction in neurodegeneration 7.