Calpain Inhibitor VI is a cell permeable peptide aldehyde which functions as a reversible calpain inhibitor. Studies indicate that Calpain Inhibitor VI strongly inhibits cathepsin B and cathepsin L. In addition, Calpain Inhibitor VI reduces nuclear opacity and proteolysis of crystallins and α-spectrin induced by A23187 . Studies suggest that substitution at the P1 position, specially a bulky amino acid residual aldehyde, will increase the potency of the Calpain Inhibitor VI. Furthermore, the S-configuration of Calpain Inhibitor VI is important in the inhibition of cathepsin L.