PSGL-1 can serve as a ligand for P-selectin (P stands for platelet), which is one of a family of selectins that includes E-selectin (endothelial) and L-selectin (leukocyte).

However, inflammation causes the expression of cell adhesion molecules (CAM) such as P-selectin on the surface of the blood vessel wall.

[citation needed] The systemic administration of soluble recombinant forms of human PSGL-1 such as rPSGL-Ig or TSGL-Ig can prevent reperfusion injury caused by leukocyte influx after an ischemic insult to various types of vascularized tissues (IRI).

The protective effects of soluble recombinant forms of PSGL-1, acting as pan-selectin antagonists, has been studied in multiple animal models of solid organ transplant and ARDS.

Consequently, the antagonsim of PSGL-1 engagement and signaling has been proposed as a promising target for future checkpoint inhibitor anti-cancer drugs.