Caspase-12 is localized to the endoplasmic reticulum (ER), but not to cytoplasm or mitochondrion. Caspase-12 is activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals. One well-known cause of ER stress in neurons is the accretion of amyloid-beta, the insoluble protein that forms plaques in the brains of patients with Alzheimer's disease. Caspase-12 mediates cytotoxicity induced by amyloid-beta and ER stress-induced apoptosis. Caspase-12 is ubiquitously expressed in tissues. Similar to other members of the Caspase family, Caspase-12 requires cleavage of the prodomain to activate its proapoptotic form.Synonyms: CASP-12, CASP12, Inactive caspase-12