Calreticulin (CALR) is a multifunctional protein that acts as a major Ca(2+)-binding (storage) protein in the lumen of the endoplasmic reticulum. It is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin binds to antibodies in certain sera of systemic lupus and Sjogren patients which contain anti-Ro/SSA antibodies, it is highly conserved among species, and it is located in the endoplasmic and sarcoplasmic reticulum where it may bind calcium. Calreticulin has an important function as a modulator of nuclear hormone receptors and their regulation of gene transcription. For example, it can inhibit the glucocorticoid receptor from binding to its specific response element. It can also inhibit the binding of androgen receptor (AR) to its hormone-responsive DNA element, and can block retinoic acid receptor transcriptional activities along with retinoic acid-induced neuronal differentiation in vivo. Calreticulin is also important for the development of the central nervous system, and it is of interest in various neurological disorders where it sees deregulated expression. In immunohistochemistry, calreticulin is a secreted protein that has strong cytoplasmic/membranous positivity in the thyroid and is weakly present in most tissues throughout the body. References: ACS Chem. Neurosci. 2019. 10 (6):2629-2646, DOI: 10.1021/acschemneuro.9b00158