Cathepsin S is a cysteine protease found in the lysosome of lymphatic cells. It is a member of the papain superfamily and has 57% identity to cathepsins L and K. Unlike most other lysosomal proteases that are only active under acidic conditions, the activity of cathepsin S exhibits a broad pH optimum that extends to alkaline pH. Cathepsin S is expressed mainly in dendritic cells, B cells, and macrophages, where cathepsin S acts as a key enzyme in major histocompatibility complex class II mediated antigen presentation (1, 2).
Cathepsin S is upregulated by IFNγ through the IFN stimulated response element in the cathepsin S promoter. This enzyme is also implicated in the pathogenesis of several diseases such as rheumatoid arthritis, multiple sclerosis (3, 4), atherosclerosis (5-7), cancer (8, 9), Alzheimer’s and Down’s Syndrome (10). It is an attractive target for drug discovery due to its involvement in immune system function as well as extracellular matrix breakdown.