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Accumulation of misfolded proteins leads to the dissociation of BiP from the three UPR sensors ( Figure 2F ) ( In addition to protein synthesis, the ER is also responsible for storage of intracellular Ca 2+ and therefore, regulates calcium-dependent signaling within the cell, such as protein folding and enzymatic function ( 2+ balance influencing multiple processes, including activation of cytosolic post-translational modification (PTM) enzymes by facilitating their translocation into subcellular compartments