Calreticulin (CALR) is a multifunctional endoplasmic reticulum (ER)-resident protein involved in calcium homeostasis, glycoprotein folding, and immune regulation. It acts as a molecular chaperone, ensuring proper protein folding, and modulates calcium signaling by binding ER luminal calcium. Beyond its intracellular roles, calreticulin can translocate to the cell surface under stress, where it interacts with immune cells, promoting phagocytosis and immunogenic cell death—a process critical in cancer immunotherapy.
Anti-calreticulin antibodies are autoantibodies targeting this protein, often linked to autoimmune diseases and certain cancers. In myeloproliferative neoplasms (MPNs), somatic mutations in *CALR* exon 9 (e.g., 52-bp deletions or insertions) drive disease pathogenesis, particularly in *JAK2/MPL*-negative primary myelofibrosis and essential thrombocythemia. These mutations alter CALR’s C-terminal domain, creating a novel epitope that may trigger immune responses. While anti-CALR antibodies are not routinely used diagnostically, their presence is explored as a biomarker for disease monitoring or therapeutic targeting.
In autoimmune contexts, anti-calreticulin antibodies are associated with systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjögren’s syndrome, though their clinical significance remains unclear. Research suggests they may contribute to inflammation by disrupting ER function or forming immune complexes. Detection methods include ELISA and indirect immunofluorescence. Further studies are needed to elucidate their pathogenic mechanisms and therapeutic potential.