The ins and outs of calreticulin: from the ER lumen to the extracellular space

Calreticulin was first isolated 26 years ago. Since its discovery as a mino r Ca(2+)binding protein of the sarcoplasmic reticulum, the appreciation of its importance has grown, and it is now recognized to be a multifunctional protein, most abundant in the endoplasmic reticulum (ER). The protein has w ell-recognized physiological roles in the ER as a molecular chaperone and C a2+-signalling molecule. However, it has also been found in other membrane- bound organelles, at the cell surface and in the extracellular environment, where it has recently been shown to exert a number of physiological and pa thological effects. Here, we will focus on these less-well-characterized fu nctions of calreticulin.