Sfrp2, or Secreted frizzled-related protein 2, is a vital molecule in the Wnt signaling pathway. It can act as an antagonist of the canonical Wnt signaling pathway and is involved in regulating multiple biological processes such as organ development and disease processes [7].

In skin, Sfrp2 defines a major fibroblast population with distinct morphology and function compared to other fibroblast populations defined by genes like FMO1. Sfrp2+ fibroblasts are small, elongated, and distributed between collagen bundles, and differential gene expression suggests their role in matrix deposition [1].

In diabetic cardiomyopathy, Sfrp2 is downregulated, and its overexpression can reverse apoptosis and promote mitochondrial function in an AMPK-PGC1-α-dependent manner, while silencing endogenous Sfrp2 promotes glucolipotoxicity-induced mitochondrial dysfunction and apoptosis [2].

In radioimmunotherapy, conditional Sfrp2 knockout in cancer-associated fibroblasts (CAFs) boosts the abscopal effect by rewiring the vascular-immune microenvironment to promote CD8+ T cell recruitment to unirradiated tumors [3].

In aged-related melanoma, aged fibroblasts secrete sFRP2, which drives melanoma metastasis and therapy resistance through a multi-step signaling cascade [4].

In systemic sclerosis skin, SSc dermal myofibroblasts arise from an SFRP2hi/DPP4-expressing progenitor fibroblast population [5].

In idiopathic pulmonary fibrosis, a fibroblast-dependent TGF-β1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia [6].

In cardiomyogenesis, Sfrp2 promotes the differentiation of multipotent cKit(+) cells into cardiomyocytes in vivo, improving cardiac function in an injury model [8].

In preeclampsia, SFRP2 overexpression in JEG-3 cells reduces cell viability, proliferation, and migration, and increases apoptosis by inhibiting the Wnt/β-catenin pathway [9].

In diabetic wound healing, suppression of SFRP2 delays the wound healing process in diabetic mice, affects macrophage infiltration and functional phenotype transition, and energy metabolism [10].

In conclusion, Sfrp2 plays diverse and crucial roles in various biological processes and disease conditions. Studies using gene knockout or conditional knockout models in mice have revealed its significance in areas such as skin fibroblast function, diabetic cardiomyopathy, cancer therapy response, melanoma metastasis, fibrosis development, cardiomyogenesis, preeclampsia, and diabetic wound healing. These findings enhance our understanding of Sfrp2's biological functions and provide potential therapeutic targets for related diseases.