In order to develop an activity assay that is more specific for caspase-6 than available methods relying on the cleavage of the VEID peptide, we decided to investigate the cleavage of known caspase-6 substrates. To be useful for the measurement of caspase-6 activity, a substrate would ideally be as specific as possible. In particular it should not be cleaved by other proteases activated during apoptosis and be cut by caspase-6 in detectable quantities. The protein substrate should be easy to purify and thus available in larger amounts, and existing neo-epitope antibodies allowing for the specific detection of the cleavage fragment would be an advantage. The nuclear lamin proteins were among the first caspase-6 substrates characterized [25] , and knockdown studies strongly suggest that their cleavage during apoptosis is highly dependent on the presence of caspase-6 [24] . Furthermore, purified lamin A as well as a variety of neo-epitope antibodies against the cleavage fragments are readily available, and high stability of the cleavage fragments without further degradation during the apoptotic process has been described [26] , which should facilitate their detection.