Calreticulin (CALR) (CALR)

Calreticulin (CALR) is a highly conserved 46 kDa protein primarily residing in the endoplasmic reticulum (ER) lumen, where it functions as a molecular chaperone and a major calcium-sequestering protein (UniProt P27797). The glycan-binding domain, composed of the N-terminal and proline-rich P-domain, specifically recognizes monoglucosylated (Glc1Man9GlcNAc2) glycoproteins, facilitating their proper folding and preventing the export of misfolded proteins (PubMed: 26433174). Beyond its ER-resident roles, calreticulin translocates to the cell surface in response to stress, acting as a critical "eat-me" signal that triggers phagocytosis by dendritic cells and promotes immunogenic cell death (PubMed: 17187058). In clinical oncology, mutations in the CALR gene (specifically exon 9) are major drivers of myeloproliferative neoplasms (MPNs), such as essential thrombocythemia, where the mutant protein binds to and constitutively activates the thrombopoietin receptor (MPL) (PubMed: 24350634). Therapeutic development focuses on monoclonal antibodies that target these mutant forms or surface-exposed calreticulin to modulate immune responses and treat hematologic malignancies (PubMed: 33619385).

Other names

CRTCRP55CalregulinHACBPERp60grp60

Inhibition of mutant CALR-mediated MPL activation; Blockade of surface CALR signaling; Enhancement of immunogenic cell death