CCN4 (also known as WISP1, cellular communication network factor 4) is a secreted matricellular cysteine-rich protein encoded on chromosome 8 that functions as a key regulator of cell-cell communication and tissue remodeling 1. As a downstream effector in Wnt/β-catenin signaling, CCN4 promotes cell proliferation, migration, and survival through integrin-dependent pathways, particularly via αvβ5 and α6β1 integrins 23. CCN4 activates PI3K/Akt signaling and NF-κB-mediated inflammatory responses, inducing expression of pro-inflammatory mediators including IL-6 and VCAM-1 32. In tissue regeneration, CCN4 controls muscle stem cell expansion through Akt signaling, and its loss during aging contributes to impaired skeletal muscle regeneration 4. Pathologically, aberrant CCN4 upregulation drives fibrosis progression in idiopathic pulmonary fibrosis and osteoarthritis-associated cartilage degeneration 56. CCN4 also promotes epithelial-mesenchymal transition in endometriosis via Wnt/β-catenin pathway activation 7. Given its broad involvement in cell proliferation, migration, angiogenesis, and inflammatory responses, CCN4 has emerged as both a disease biomarker and therapeutic target across cancer, fibrosis, metabolic, and inflammatory disorders 1.