CST1 (cystatin SN) is a cysteine protease inhibitor belonging to the type 2 cystatin family, primarily expressed in salivary glands, lacrimal glands, and respiratory epithelium 1. It functions as a suppressor of cysteine protease activity, particularly inhibiting allergen-derived proteases from house dust mites (HDM) 2. In allergic airway disease, CST1 protects epithelial barrier integrity by counteracting HDM-induced cysteine protease activity that disrupts tight junctions 2. CST1 expression is elevated in asthma and allergic rhinitis, where it serves as a biomarker of Th2-mediated inflammation and correlates with disease severity 23. Notably, CST1 is the only gene upregulated in both upper and lower airways in allergic disease patients and shows excellent diagnostic efficiency for distinguishing Th2-high asthma 3. Beyond allergic disease, CST1 plays a tumor-promoting role in esophageal squamous cell carcinoma, where it enhances cell migration and invasion through MEK/ERK/CREB pathway activation, and is regulated by miR-942-5p 45. These findings suggest CST1 has dual functionality: protective in allergic airway inflammation and pathogenic in cancer progression, making it a potential therapeutic target across distinct disease contexts.