Calnexin (CNX), an abundant ~90kD molecular chaperone, is a unglycosylated resident ER transmembrane protein. In mammalian cells, calnexin, together with calreticulin (CRT), plays a key role in glycoprotein folding and its control within the ER, by interacting with folding intermediates via their monoglucosylated glycans. Calnexin associates with newly synthesized monomeric glycoproteins and only recognizes glycoproteins when they are incompletely folded. Calnexin associates with numerous oligomeric protein complexes within the ER, including beta1 and alpha6 integrins, major histocompatibility class I and class II molecules, the antigen receptors expressed on T and B lymphocytes, human thyroperoxidase (hTPO), and acetylcholine receptor. Recent data also suggest that calnexin might be responsible for the prolonged retention of pro-alpha6 integrin within ER compartment. Furthermore, calnexin has been demonstrated to function as a bonafide molecular chaperone capable of interacting with polypeptide segments of folding glycoproteins.