The SELPLG gene encodes P-selectin glycoprotein ligand-1 (PSGL-1), a transmembrane, disulfide-linked homodimeric mucin-like glycoprotein primarily expressed on hematopoietic cells, including all leukocytes (neutrophils, monocytes, and T/B lymphocytes) and stimulated T cells ^[1]. Its main function is to act as a high-affinity counter-receptor for the adhesion molecules P-, E-, and L-selectin, playing a critical role in leukocyte trafficking by mediating the tethering and rolling of immune cells on activated endothelium and platelets during inflammation and immune surveillance. PSGL-1 requires post-translational modifications, specifically tyrosine sulfation and the addition of the sialyl Lewis x tetrasaccharide, for its high-affinity selectin binding ^[2]. Beyond adhesion, PSGL-1 is also a recently recognized immune checkpoint that acts as a negative regulator of T-cell function, dampening T-cell receptor (TCR) signaling and promoting T-cell exhaustion in contexts like chronic viral infection and cancer. Associated diseases include a variety of cancers (e.g., Multiple Myeloma, Acute Myeloid Leukemia, Anaplastic Large T-cell Lymphoma), where its expression can promote metastasis and chemoresistance, as well as inflammatory conditions like Acute Respiratory Distress Syndrome (ARDS) and atherosclerosis, due to its role in leukocyte recruitment and inflammation, and certain viral infections (e.g., Enterovirus 71) where it can act as a receptor ^[3].

B6-huPSGL-1 (huSELPLG) mouse is a humanized model generated using gene editing technology, in which the mouse Selplg endogenous extracellular domain is replaced with the human SELPLG extracellular domain. The murine signal peptide is preserved. This model can be used for studying the pathological mechanisms and therapeutic approaches of various cancers, inflammatory conditions, and certain viral infections (e.g., Enterovirus 71), as well as for the development of SELPLG-targeted drugs.