SFRP1 is a secreted modulator of Wnt signaling that functions as a context-dependent regulator of cell proliferation, differentiation, and tissue remodeling. Mechanistically, SFRP1 decreases intracellular β-catenin levels and inhibits WNT1/WNT4-mediated transcription 1. In pulmonary fibrosis, SFRP1 expression marks a transitional fibroblast state that precedes myofibroblast conversion; TGFβ1 downregulates SFRP1 and induces fibroblast invasion through RHOA pathway modulation 1. Fibroblast-derived extracellular vesicles enriched in SFRP1 potentiate lung fibrosis by activating WNT/β-catenin signaling in alveolar epithelial cells, and Sfrp1 deficiency inhibits fibrogenesis 2. In colorectal cancer, inflammatory CAF-derived SFRP1 binds FGFR2 to activate HIF1 signaling, promoting tumor stemness, EMT, and liver metastasis 3. Following peripheral nerve injury, Schwann cell-secreted SFRP1 engages macrophage HSP90, triggering dysregulated inflammation and nerve degeneration 4. In eosinophilic esophagitis, IL-13-induced STAT3-dependent SFRP1 expression promotes epithelial proliferation 5. SFRP1 exhibits dual roles in cancer: epigenetic silencing via promoter methylation associates with increased RCC risk and poor prognosis 6, yet tumor-derived SFRP1 can suppress colorectal cancer progression by remodeling CAF phenotypes 7. These findings establish SFRP1 as a pleiotropic regulator with therapeutic potential across fibrotic, inflammatory, and malignant diseases.