Cystatin B also known as CSTB is a stefin that functions as an intracellular thiol protease inhibitor. Cystatin B plays a crucial role as a thiol protease inhibitor, forming complexes with proteases such as papain and cathepsins B, H, and L, which are essential for protein degradation and turnover within cells. Cystatin B is primarily located in the cytoplasm and is significantly expressed in the heart, liver, and kidney, where cystatin B serves to protect against the leakage of intracellular proteases from lysosomes, thereby maintaining cellular integrity and function. Dysregulation of cystatin B has been implicated in various pathological conditions, including neurodegenerative diseases, highlighting cystatin B′s importance in cellular homeostasis and potential as a therapeutic target.