CST2 (cystatin SA) is a cysteine protease inhibitor 1 that functions as a thiol protease inhibitor with selective activity against different cysteine proteases. The protein exists in two allelic variants (SA1 and SA2) encoding different amino acid sequences, with the QXVXG hairpin loop region critical for protease inhibition specificity 2. CST2 shows differential inhibitory potency against various cathepsins, with SA2 variant displaying substantially reduced inhibitory capacity against papain, ficin, and cathepsin K compared to SA1 2. Biologically, CST2 is significantly overexpressed in multiple malignancies including esophageal squamous cell carcinoma and gastric adenocarcinoma, where it promotes tumor progression 13. In esophageal cancer, CST2 knockdown reduces proliferation, migration, and invasion while decreasing tumor burden in vivo 1. CST2 facilitates pancreatic cancer malignancy through PI3K/AKT pathway activation, with transcription factor RUNX1 positively regulating CST2 expression 4. High CST2 expression independently predicts poor disease-specific and disease-free survival in esophageal cancer 1. Additionally, CST2 is upregulated in nasal epithelial myoepithelial and mucus-secretory cells in asthmatic youth, correlating with elevated total IgE levels 5. These findings establish CST2 as a potential tumor immune biomarker and therapeutic target across multiple cancer types.