DKK2 is a secreted protein that functions as a canonical Wnt signaling inhibitor by forming complexes with LRP5/6 receptors and promoting their internalization 1. In cancer contexts, DKK2 exhibits complex roles: it promotes colorectal cancer progression by accelerating aerobic glycolysis and stimulating VEGF-independent angiogenesis through lactate production 2. Additionally, DKK2 can function as a tumor suppressor in some contexts, where its inhibition by bacterial metabolites leads to enhanced Wnt/β-catenin signaling and increased cancer cell proliferation 3. The protein also modulates immune responses, with NAT10-mediated DKK2 mRNA stabilization leading to CD8+ T cell dysfunction through cholesterol accumulation 4. In neurological contexts, DKK2 is upregulated in activated microglia during neurodegeneration and can block dendritic spine formation, contributing to synaptic dysfunction 5. During development, DKK2 serves as an arterial endothelial cell marker, indicating its role in vascular specification 6. In stroke pathology, elevated DKK2 levels correlate with worse outcomes by impairing neurovascular Wnt signaling and blood-brain barrier integrity 1. The protein's expression is regulated by epigenetic mechanisms including DNA methylation and histone modifications 73.