CALR编码蛋白是钙网蛋白，是位于内质网腔（ER）中的钙结合蛋白。在ER中，CALR蛋白具有两个主要功能：蛋白质折叠途径中的分子伴侣和钙稳态调节剂。其作为分子伴侣，CALR起到防止部分或错误折叠的蛋白质从ER到高尔基体的聚集和输出的作用；CALR及其旁系同源物CNX（钙联接蛋白）的活性对于确保糖蛋白质量很重要，包括膜结合蛋白，转运蛋白和某些分泌因子。另外，CALR定位于细胞核并起抑制核激素受体的功能，例如雄激素和糖皮质激素受体，表明在转录调节中起作用。CALR在免疫调节中也具有重要作用，包括折叠MHC I类分子并在癌细胞上作为“吃我”信号。在具有缺乏JAK2或MPL改变的骨髓增生性肿瘤的患者中检测到了CALR的复发性体细胞突变，表明CALR在JAK-STAT信号传导途径的激活中起作用。CALR在包括骨髓增生性肿瘤在内的各种实体瘤和血液恶性肿瘤中发生改变。

CALR, also known as calreticulin, is a calcium-binding protein located in the lumen of the endoplasmic reticulum (ER). In the ER, the CALR protein has two primary functions: molecular chaperone in the protein-folding pathway and regulator of calcium homeostasis the Golgi. The activity of CALR and its paralog CNX (calnexin) is important to ensure the quality of glycoproteins, including membrane-bound proteins, transporters and certain secreted factors. Additionally, CALR is localized to the nucleus and inhibits the function of nuclear hormone receptors, such as the androgen and glucocorticoid receptors, suggesting a role in transcriptional regulation. CALR also has important roles in immune regulation including folding of MHC Class I molecules and serving as an “eat me” signal on cancer cells. Recurrent somatic mutations in CALR have been identified in patients with myeloproliferative neoplasms that lack alterations in JAK2 or MPL, suggesting a role in activation of the JAK-STAT signaling pathway. Alterations in CALR commonly occur as frameshift mutations in the C-terminal region of CALR, truncating the ER-targeting domain of the protein. CALR mutations disrupt the interaction between CALR and membrane receptors (such as MPL) and activate downstream signaling pathways. Somatic CALR mutations are also found in familial cases of thrombocythemia or primary myelofibrosis.

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