SFRP2 (secreted frizzled-related protein 2) is a soluble modulator of Wnt signaling that functions primarily through direct interaction with Wnt ligands 1. In normal skin, SFRP2 defines a major fibroblast population characterized by small, elongated morphology distributed between collagen bundles, suggesting roles in matrix deposition 2. SFRP2+ fibroblasts exhibit remarkable plasticity across disease states: in psoriasis, they transition to pro-inflammatory states producing chemokines (CCL13, CCL19, CXCL12) and cathepsin S that amplify immune responses 3. In cancer, SFRP2+ cancer-associated fibroblasts (CAFs) promote malignant progression, induce immunosuppressive Tregs, and correlate with chemotherapy resistance 4. During colorectal cancer metastasis, malignant epithelial cells transdifferentiate into SFRP2+ CAFs through BHLHE40-driven EMT 5. In radioimmunotherapy, tumor-secreted PAI-1 triggers pericyte-to-SFRP2high CAF conversion via LRP1/p65 signaling, suppressing anti-tumor immunity 6. In idiopathic pulmonary fibrosis, fibroblast-derived sFRP2 activates non-canonical Wnt/Fzd5/calcineurin signaling in alveolar epithelial cells, promoting pathogenic epithelial metaplasia 7. In uterine scarring, sFRP2 overexpression drives fibrotic transformation through non-canonical Wnt pathway activation 8. These findings establish SFRP2 as a critical stromal regulator linking fibroblast identity, pathological remodeling, and immunomodulation across multiple tissues.