Swine Osteopontin (OPN) (also known as SPP1, Secreted Phosphoprotein 1, bone sialoprotein I, ETA-1, or early T-lymphocyte activation-1) is a multifunctional phosphorylated glycoprotein involved in immune regulation, cell adhesion, and tissue remodeling in pigs (Sus scrofa domesticus). Osteopontin interacts with integrins (such as αvβ3, αvβ1, and α4β1) and CD44 receptors, activating signaling pathways that regulate cell migration, inflammatory responses, and extracellular matrix remodeling. In pigs, OPN is produced by osteoblasts, macrophages, epithelial cells, and activated T lymphocytes, and plays roles in bone metabolism, immune responses, and tissue repair. In swine health, osteopontin is particularly relevant in reproductive biology, where it is expressed in the uterine endometrium and conceptus during early pregnancy, contributing to embryo implantation, placental attachment, and maternal–fetal communication. OPN is also involved in immune responses during respiratory and enteric infections, including conditions such as porcine reproductive and respiratory syndrome virus (PRRSV) and bacterial infections, where it can influence leukocyte recruitment and inflammatory signaling. While osteopontin supports immune defense and tissue repair, excessive expression may contribute to chronic inflammation or fibrotic tissue remodeling. Because pigs are widely used as large-animal models for human physiology, immunology, and reproductive biology, characterization of swine osteopontin supports studies of immune regulation, implantation biology, tissue remodeling, and host–pathogen interactions relevant to both veterinary medicine and translational biomedical research.