Sortilin (SORT1) (SORT1)

Sortilin, also known as SORT1 or Neurotensin receptor 3 (NTR3), is a type I transmembrane protein belonging to the Vps10p domain-containing receptor family. It primarily functions as a sorting receptor in the trans-Golgi network, directing proteins to the lysosome or secretory pathway, and as a clearance receptor on the cell surface that internalizes ligands via endocytosis [7, 34]. In the field of targeted protein degradation (TPD), Sortilin has been identified as a tumor-enriched sorting receptor that can be co-opted to shuttle extracellular or membrane-bound proteins to the lysosome for degradation [7, 18, 33]. This is exemplified by the MedTAC (mRNA-encoded lysosomal targeting chimera) platform, which uses Sortilin to route oncogenic proteins like PTK7 to lysosomes for degradation [7, 29]. Sortilin is overexpressed in several malignancies, including breast, ovarian, and lung cancers, making it an attractive target for both direct inhibition and as a vehicle for the targeted delivery of degraders or cytotoxic payloads [7, 33].

Other names

Neurotensin receptor 3NTR3Gp95100 kDa neurotensin receptorTumor-enriched sorting receptorTumor-enriched degrader receptor

Acts as a lysosomal targeting receptor (LTR) that mediates the internalization and trafficking of target proteins to the lysosome for degradation, particularly in the context of MedTAC and LYTAC technologies [7, 18, 29].