PVR/CD155 is a transmembrane glycoprotein belonging to the immunoglobulin superfamily, serves as the primary receptor for poliovirus, facilitating viral entry into host cells. CD155′s structure contains multiple immunoglobulin-like domains that contribute to binding affinity for poliovirus serotypes 1, 2, and 3, which utilize a shared mechanism for cell entry. CD155 is involved in cell-matrix interactions through binding to vitronectin, a matrix protein that plays a significant role in cell adhesion and migration. Soluble isoforms of CD155 in human serum and cerebrospinal fluid, including alpha, beta, and gamma forms, highlight functional diversity and regulatory potential in immune responses. These soluble forms can inhibit poliovirus entry by competing with the membrane-bound receptor, underscoring their importance in modulating viral infections and maintaining cellular homeostasis.