DSTN (destrin) is an actin-depolymerizing protein that plays critical roles in cytoskeletal dynamics and cellular function. The protein severs actin filaments (F-actin) and binds to actin monomers (G-actin) in a pH-independent manner, serving as a key regulator of actin dynamics 1. DSTN functions as a negative feedback inhibitor of smooth muscle cell differentiation by regulating serum response factor (SRF)-dependent gene expression, with its expression controlled by RhoA and TGF-β signaling pathways 1. Mechanistically, DSTN associates with and facilitates nuclear translocation of β-catenin, activating Wnt/β-catenin signaling to promote epithelial-to-mesenchymal transition 23. Clinically, DSTN demonstrates significant disease relevance across multiple pathologies. High DSTN expression correlates with poor prognosis in lung adenocarcinoma and promotes cancer cell proliferation, invasion, and metastasis 2. DSTN hypomethylation contributes to radiotherapy resistance in rectal cancer by activating Wnt/β-catenin signaling 3. Conversely, severe DSTN deficiency causes corneal epithelial defects and leads to autoinflammatory conditions through upregulation of inflammatory chemokines like CXCL5 4. The protein has emerged as a potential biomarker and therapeutic target in various diseases including NAFLD, head and neck squamous cell carcinoma, atherosclerosis, and pulmonary hypertension 5678.