Increases in both endogenous and exogenous 4-HNE, combined with age-dependent ischemia, may overactivate μ-calpain, which can cleave the lysosomal stabilizer protein, Hsp70.1, especially after it is carbonylation by ROS, and thus induce lysosome-mediated cell death via the cathepsin leakage. Here, CAPN2 is linked to ischemia.