Interactions of intercellular adhesion molecules of the selectin family with glycoconjugates of cell membranes mediate the initial stage of the adhesion cascade, which recruits leukocytes circulating in the bloodstream to sites of infection or damage. The formation of heterotypic cell aggregates between individual cells of hematopoietic and non-hematopoietic origin may be involved in processes leading to inflammation, thrombosis, and metastasis. A key protein, the dimeric glycoprotein PSGL-1, a P-selectin glycoprotein ligand, plays an important role in the binding of selectins, serving as a ligand for all three selectins. PSGL-1 combines signals activating various biochemical pathways during binding and rolling of leukocytes. The integration of these signals leads to activation of leukocytes, integrin-mediated arrest, restructuring of the cyto- skeleton of interacting cells, polarization, and subsequent diapedesis of leukocytes into surrounding tissues. The multilevel effect of PSGL-1 on cellular traffic in the physiological and inflammatory states is largely determined by posttranslational modifications, among which an important place is given to specific O- and N-glycosylation and sulfation. In this review, we discuss modifications of PSGL-1 associated with the initiation of biochemical pathways, as well as its interactions, which make it possible to classify this molecule as signaling, paying special attention to the mechanisms leading to pathology, including cardiovascular.