CTSL and dilated cardiomyopathy: Mice lacking CTSL spontaneously developed heart disease at 1 year of age that resembled many features of human dilated cardiomyopathy.12–13 We have previous shown that deficiency of lysosomal enzyme CTSL in the setting of ischemic injury caused exaggerated activation of UPS.14 We believe that CTSL, an important lysosomal protein–processing enzyme, may play a key role in maintaining the lysosomal degradation response to stress.