The endoplasmic reticulum is a major Ca2+ store of the cell that impacts many cellular processes within the cell. The endoplasmic reticulum has roles in lipid and sterol synthesis, protein folding, post-translational modification and secretion and these functions are affected by intraluminal endoplasmic reticulum Ca2+. In the endoplasmic reticulum there are several Ca2+ buffering chaperones including calreticulin, Grp94, BiP and protein disulfide isomerase. Calreticulin is one of the major Ca2+ binding/buffering chaperones in the endoplasmic reticulum. It has a critical role in Ca2+ signalling in the endoplasmic reticulum lumen and this has significant impacts on many Ca2+-dependent pathways including control of transcription during embryonic development. In addition to Ca2+ buffering, calreticulin plays important role in the correct folding and quality control of newly synthesized glycoproteins.