Caspase-6 has recently emerged as an important player in neuronal dysfunction and degeneration and its activation has been linked to several neurodegenerative conditions such as AD, HD and stroke [16, 17, 18, 19, 20, 21, 22, 30, 37] . Direct inhibition of the enzyme as well as targeting of other players in the activation pathway might therefore be beneficial in these disorders. We show here that the cleavage of lamin A can be assessed in a highthroughput setting using a high-content imaging platform, making it an ideal intracellular readout to test interventions that decrease caspase-6 activity.