DKK1 (dickkopf Wnt signaling pathway inhibitor 1) is a secreted antagonist of canonical Wnt signaling that functions as a key regulator of both developmental processes and disease pathogenesis. Mechanistically, DKK1 inhibits Wnt/β-catenin signaling by binding to the co-receptor LRP5/6 and forming a ternary complex with KREMEN that promotes LRP5/6 internalization 1. During embryonic development, DKK1 regulates antero-posterior axial patterning, limb development, somitogenesis, and cardiogenesis through Wnt antagonism 23. In adult pathology, DKK1 has emerged as a critical immunosuppressive factor. DKK1 promotes tumor immune evasion across multiple cancer types by inducing macrophages to suppress CD8+ T cell and natural killer cell activity, thereby limiting anti-PD-1 immunotherapy efficacy 456. Additionally, DKK1 coordinates inflammatory responses through cell-autonomous mechanisms involving SOCS3-restricted RelA activity 7. In non-cancer contexts, DKK1 loss promotes endometrial fibrosis via autophagy dysregulation and exosome-mediated macrophage differentiation, contributing to intrauterine adhesions 8. DKK1 inhibition emerges as a therapeutic strategy: anti-DKK1 treatment enhances chemotherapy and immunotherapy efficacy in multiple cancers while simultaneously alleviating chemotherapy-induced peripheral neuropathy 96.