Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum

Calreticulin is an ER (endoplasmic reticulum) luminal Ca²⁺-buffering chaperone. The protein is involved in regulation of intracellular Ca²⁺ homoeostasis and ER Ca²⁺ capacity. The protein impacts on store-operated Ca²⁺ influx and influences Ca²⁺-dependent transcriptional pathways during embryonic development. Calreticulin is also involved in the folding of newly synthesized proteins and glycoproteins and, together with calnexin (an integral ER membrane chaperone similar to calreticulin) and ERp57 [ER protein of 57 kDa; a PDI (protein disulfide-isomerase)-like ER-resident protein], constitutes the ‘calreticulin/calnexin cycle’ that is responsible for folding and quality control of newly synthesized glycoproteins. In recent years, calreticulin has been implicated to play a role in many biological systems, including functions inside and outside the ER, indicating that the protein is a multi-process molecule. Regulation of Ca²⁺ homoeostasis and ER Ca²⁺ buffering by calreticulin might be the key to explain its multi-process property.