Cystatin F is a recently discovered type II cystatin expressed almost exclu-sively in immune cells. It is present intracellularly in lysosome-like vesicles, which suggests a potential role in regulating papain-like cathepsins involved in antigen presentation. Therefore, interactions of cystatin F with several of its potential targets, cathepsins F, K, V, S, H, X and C, were studied in vitro. Cystatin F tightly inhibited cathepsins F, K and V with Ki values ranging from nmto nm, whereas cathepsins S and H were inhib-ited with 100-fold lower affinities (Ki 30 nm). The exopeptidases, cathep-sins C and X were not inhibited by cystatin F
