Periostin (POSTN) is a secreted extracellular matrix protein that promotes cell adhesion and migration through interactions with integrin receptors. It induces cell attachment and spreading 1 and functions as a ligand for α(V)β(3) and α(V)β(5) integrins, supporting adhesion of epithelial cells. The protein also enhances incorporation of BMP1 in the fibronectin matrix and facilitates subsequent proteolytic activation of lysyl oxidase, contributing to connective tissue organization. POSTN plays a central role in fibrotic and inflammatory diseases. In idiopathic pulmonary fibrosis, POSTN is upregulated in fibroblasts and its knockdown attenuates fibrotic marker expression 2. In the cardiac setting, POSTN+ fibroblasts emerge from FAP+ fibroblast lineages through IL-1β signaling between macrophages and fibroblasts, and blocking IL-1β signaling reduces myocardial fibrosis and improves cardiac function 3. In doxorubicin-induced cardiomyopathy, CD47 antibody neutralization prevents cardiac dysfunction and fibrosis by clearing POSTN+ activated fibroblasts 4. In cancer, POSTN+ cancer-associated fibroblasts form immune-suppressive microenvironments that limit therapeutic efficacy. In hepatocellular carcinoma and non-small cell lung cancer, POSTN+ CAFs recruit SPP1+ macrophages and inhibit T-cell infiltration, reducing immunotherapy responsiveness 5 6. In papillary thyroid cancer, CAF-derived POSTN promotes tumor growth through integrin-FAK-STAT3 signaling 7. These findings position POSTN as a target for anti-fibrotic and cancer immunotherapy strategies.