RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a membrane-bound glycoprotein with dual roles in cell signaling and protease regulation. In the central nervous system, RECK functions as a Wnt7-specific co-receptor that enables brain endothelial cells to selectively respond to Wnt7a/b ligands 1. RECK binds with low micromolar affinity to the disordered linker region of Wnt7, conferring ligand selectivity 12. RECK then works together with the adhesion GPCR Gpr124 to deliver Wnt7-bound ligands to Frizzled receptors, assembling higher-order signaling complexes essential for CNS angiogenesis and blood-brain barrier regulation 13. As a serine protease inhibitor, RECK negatively regulates matrix metalloproteinases (MMPs), suppressing MMP9 secretion and inhibiting its enzymatic activity, while also inhibiting MMP2 and MMP14 4. This MMP inhibition is critical for maintaining extracellular matrix integrity and preventing tumor progression and angiogenesis 4. RECK is downregulated in cancers via RAS oncogene signaling and miR-21-5p delivery 45. RECK expression correlates with cancer survival prognosis and drug sensitivity across multiple cancer types 6. Additionally, RECK modulates endoplasmic reticulum stress in tumor cells, making it a potential therapeutic target 7.