Extracted from the Mediterranean plant Thapsia garganica ("deadly carrot"), thapsigargin is a guaianolide sesquiterpene lactone that binds SERCA pumps in their calcium-free E2 state with sub-nanomolar affinity.
By blocking Ca²⁺ reuptake into the endoplasmic and sarcoplasmic reticulum while passive ER leak continues, thapsigargin rapidly empties ER lumenal Ca²⁺ stores, elevates cytosolic Ca²⁺, and triggers store-operated calcium entry (SOCE) via STIM1/Orai1.
Sustained ER calcium depletion by thapsigargin blocks chaperone-assisted protein folding, making it a benchmark experimental inducer of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).