How does thapsigargin affect the endoplasmic reticulum?

Thapsigargin is an irreversible inhibitor of sarco endoplasmic reticulum Ca2 ATPase (SERCA). It contributes to ER stress by depleting calcium stores in the lumen of the endoplasmic reticulum while increasing calcium levels in the surrounding cytoplasm. Thapsigargin also disrupts the mechanisms of autophagy. The increased cytoplasmic calcium levels and impaired autophagy leads to endoplasmic reticulum stress. Uncontrolled or severe ER stress can eventually result in apoptosis and cell death.