Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology

Osteopontin (OPN), encoded by the SPP1/Spp1 gene, is increasingly recognized as an extracellular matrix-associated immunoregulatory molecule in the central nervous system (CNS). In CNS-related contexts, OPN does not act as a uniformly protective or detrimental factor. Instead, its effects depend on the producing cell type, molecular form, receptor axis, disease stage, and lesion compartment. Accumulating evidence indicates that OPN may participate in reparative processes, including tissue preservation, debris clearance, vascular remodeling, and support of myelin-related repair, while sustained or ectopic OPN activity may contribute to synaptic injury, persistent glial reactivity, remyelination failure, and immunosuppressive tumor progression. In this review, we summarize the molecular basis of SPP1/Spp1 expression and OPN protein signaling, with emphasis on isoforms, proteolytic processing, receptor usage, and secreted versus intracellular OPN. We then discuss its roles in CNS development, chronic neurological diseases, acute CNS injury, and neuro-oncology, and highlight the need to distinguish biomarker associations, omics-based candidate pathways, and functionally validated mechanisms when considering OPN-related diagnostic or therapeutic strategies.