SPP1 and brain neoplasm: In glioblastoma (GBM), CD44 s extracellular domain directly interacts with hyaluronic acid (HA) and other matrix factors, facilitating the migration of GBM cells.28 Moreover, CD44 can also interact with other ligands, such as osteopontin, collagen, and matrix metalloproteinases (MMPs).29 These interactions contribute to the invasive and metastatic properties of GBM cells, making CD44 a key player in the aggressive behavior of this deadly brain tumor.