Calretinin, a calcium-binding protein with a molecular weight of 29kD, is a member of the large family of EF-hand proteins that also include S-100 protein. EF-hand proteins are characterized by a helix-loop-helix fold that acts as the calcium-binding site. Calretinin contains six such EF-hand stretches. It is abundantly expressed in central and peripheral neural tissues especially in the retina and neurons of the sensory pathways. Calretinin is also consistently expressed in normal and reactive mesothelial cell lining of all serosal membranes, eccrine glands of skin, convoluted tubules of kidney, Leydig and Sertoli cells of the testis, endometrium and ovarian stromal cells and adrenal cortical cells. Calretinin is also a sensitive and specific indicator of normal and reactive mesothelial cells in effusion cytology. This antibody is useful as part of an immunohistochemical marker panel to distinguish mesothelioma from adenocarcinoma. The combination of calretinin and E-Cadherin was shown to have high sensitivity and specificity in differentiating malignant mesothelioma from metastatic adenocarcinoma to the pleura in one study.