DKK3 (dickkopf-3) is a secreted glycoprotein that functions as an antagonist of canonical Wnt/β-catenin signaling by inhibiting LRP5/6 interaction with Wnt ligands and promoting LRP5/6 internalization via KREMEN-mediated mechanisms 1. During development, DKK3 regulates critical processes including axial patterning and limb formation. In adult tissues, DKK3 exhibits context-dependent roles. In inflammatory diseases, DKK3+ fibroblasts represent a pro-resolving phenotype that suppresses inflammation and promotes tissue repair 23. However, in chr11 kidney disease (CKD), DKK3 promotes pathological renal fibrosis by activating the Wnt/β-catenin pathway, enhancing mitochondrial fission through MFF upregulation, and increasing oxidative stress 4. DKK3 is also upregulated in COPD-associated sarcopenia, where it induces muscle atrophy via CKAP4-dependent mitochondrial dysfunction 5. Clinically, elevated urinary and plasma DKK3 levels serve as diagnostic biomarkers for CKD progression and sarcopenia in COPD patients 65. In rheumatoid arthritis, DKK3+ fibroblasts mark refractory disease states resistant to biologic therapies, while CD200+DKK3+ fibroblasts associate with disease remission 73. These findings position DKK3 as both a prognostic biomarker and potential therapeutic target across multiple disease contexts.