PSGL1

PSGL-1, or P-selectin glycoprotein ligand-1, is a cell surface glycoprotein of the selectin ligand family. In humans, it is encoded by the SELPLG gene and is expressed primarily on leukocytes, including neutrophils, monocytes, and subsets of lymphocytes. It is a type I transmembrane protein with a mucin-like N-terminal region that is heavily O-glycosylated and rich in serine and threonine residues, a single-pass transmembrane domain, and a cytoplasmic tail that contains tyrosine sulfation sites, which are important for ligand activity.

PSGL-1 acts as the principal ligand for P-selectin and also binds E-selectin when appropriately modified. The interaction requires post-translational modifications, including sialylated and fucosylated O-glycans (such as sialyl-Lewis X) and tyrosine sulfation, which together confer high-affinity binding. This enables leukocytes to tether and roll along activated endothelium and platelets and thereby participate in leukocyte recruitment to sites of inflammation.

Through its role in the adhesion cascade, PSGL-1 contributes to inflammatory responses, neutrophil and monocyte extravasation, and coordination of immune cell trafficking. It may also influence interactions between leukocytes and platelets in thrombo-inflammatory settings.

The SELPLG gene has been studied as a potential target to modulate inflammatory cell recruitment. Alterations in PSGL-1 function or expression have been investigated in the context of inflammatory diseases, infections, and cancer, and animal models lacking PSGL-1 show reduced leukocyte recruitment.