This study identifies and characterizes FSP1, a fibroblast-specific protein, as a marker for fibroblasts. Using subtractive and differential hybridization, researchers compared transcriptomes of murine fibroblasts and isogenic epithelial cells, identifying FSP1 as a novel, fibroblast-specific gene. FSP1 encodes a calcium-binding protein associated with fibroblasts and is expressed in fibroblasts but not in epithelial cells, mesangial cells, or embryonic endoderm. FSP1 is first detected during postgastrulation development and is associated with mesenchymal-origin cells. Polyclonal antiserum against FSP1 specifically stains fibroblasts, not epithelial cells, and is expressed in fibroblasts during kidney fibrosis. FSP1 is highly specific for fibroblasts and is associated with the conversion of epithelial cells to a fibroblast phenotype. In vitro, overexpression of FSP1 in tubular epithelium leads to a mesenchymal phenotype, characterized by a fibroblast-like appearance, reduced cytokeratin, and increased vimentin. Similarly, tubular epithelium submerged in collagen gels also undergoes a fibroblast-like conversion. These findings suggest that FSP1 may play a role in the transition from epithelial to fibroblast cells. The FSP1 promoter is active in fibroblasts but not in non-fibroblast cells, indicating a fibroblast-specific promoter. FSP1 is expressed in various tissues, including lung, kidney, and spleen, but not in heart and liver. In developing tissues, FSP1 is expressed in decidual cells, certain areas of the yolk sac, and perivascular cells. In mouse embryos, FSP1 is expressed in the periodontal mesenchyme, leptomeningeal membrane, and other regions. The study highlights the importance of FSP1 as a marker for fibroblasts and its potential role in fibrogenesis and cell fate mapping. FSP1 is a reliable marker for identifying fibroblasts in various tissues and may be useful in studying fibrosis and tumor metastasis. The findings suggest that fibroblasts may arise from epithelial cells in certain conditions, and FSP1 may be involved in this process. The study also emphasizes the functional heterogeneity of fibroblasts and their role in tissue repair and disease.This study identifies and characterizes FSP1, a fibroblast-specific protein, as a marker for fibroblasts. Using subtractive and differential hybridization, researchers compared transcriptomes of murine fibroblasts and isogenic epithelial cells, identifying FSP1 as a novel, fibroblast-specific gene. FSP1 encodes a calcium-binding protein associated with fibroblasts and is expressed in fibroblasts but not in epithelial cells, mesangial cells, or embryonic endoderm. FSP1 is first detected during postgastrulation development and is associated with mesenchymal-origin cells. Polyclonal antiserum against FSP1 specifically stains fibroblasts, not epithelial cells, and is expressed in fibroblasts during kidney fibrosis. FSP1 is highly specific for fibroblasts and is associated with the conversion of epithelial cells to a fibroblast phenotype. In vitro, overexpression of FSP1 in tubular epithelium leads to a mesenchymal phenotype, characterized by a fibroblast-like appearance, reduced cytokeratin, and increased vimentin. Similarly, tubular epithelium submerged in collagen gels also undergoes a fibroblast-like conversion. These findings suggest that FSP1 may play a role in the transition from epithelial to fibroblast cells. The FSP1 promoter is active in fibroblasts but not in non-fibroblast cells, indicating a fibroblast-specific promoter. FSP1 is expressed in various tissues, including lung, kidney, and spleen, but not in heart and liver. In developing tissues, FSP1 is expressed in decidual cells, certain areas of the yolk sac, and perivascular cells. In mouse embryos, FSP1 is expressed in the periodontal mesenchyme, leptomeningeal membrane, and other regions. The study highlights the importance of FSP1 as a marker for fibroblasts and its potential role in fibrogenesis and cell fate mapping. FSP1 is a reliable marker for identifying fibroblasts in various tissues and may be useful in studying fibrosis and tumor metastasis. The findings suggest that fibroblasts may arise from epithelial cells in certain conditions, and FSP1 may be involved in this process. The study also emphasizes the functional heterogeneity of fibroblasts and their role in tissue repair and disease.