To be able to accurately quantify the activity of caspase-6 in cell culture, we therefore developed novel activity assays based on the cleavage of the caspase-6 specific substrate protein lamin A [24] . Here, we confirm the specificity of lamin A cleavage by caspase-6 using C6wt and C6ko MEFs that were stressed with staurosporine to undergo apoptosis. Although the antibodies we used in this study cross-react with cleaved lamin C, specificity for caspase-6 cleavage is maintained, since both proteins arise from the same gene by alternative splicing, contain the same caspase-6 cleavage site and only differ in their C-termini with lamin A being 10 kDa longer (Fig. 2D) [28, 33] . The cleaved fragment was detected in C6wt, but not in C6ko MEFs, and we developed an electrochemiluminescence-based ELISA method to accurately quantify cleaved lamin using the Mesoscale platform. The new method has an improved detection limit and signal-noise ratio over commercially available caspase-6 activity assays using the VEID peptide substrate. Furthermore, our assay is specific to caspase-6 and thus superior for the detection of caspase-6 activity in complex samples with a variety of different proteolytic activities such as cell lysates. Through spiking with purified lamin A protein, the assay can be applied to samples lacking endogenous lamin A and C such as embryonic primary neurons. Furthermore, the method is amenable to samples where caspase-6 activity does not lead to the cleavage of the endogenous nuclear lamins and is therefore not necessarily associated with apoptosis.