Calnexin is a type I transmembrane endoplasmic reticulum chaperone protein involved in the folding and assembly of numerous proteins. Calnexin is comprised of 537 amino acids with a large luminal domain consisting of 462 amino acids. Calnexin does not possess N-linked glycosylation sites and is localized to the endoplasmic reticulum by a –RKPRRE motif at its carboxyl terminus. Calnexin is one of the few ER membrane proteins that can be phosphorylated in a GTP-dependent manner¹.

Calnexin interacts with a number of ER membrane channels. It interacts transiently with wild-type Shaker K⁺ channel in the ER but fails to associate with an unglycosylated Shaker mutant that makes active, cell surface channels. This suggest that glycosylation of Shaker protein is required for interaction with calnexin but calnexin is not required for the proper assembly and folding of Shaker channels².

Coexpression of calnexin with the voltage-gated potassium channel K_V1.2α was found to produce a substantial dose-dependent increase in cell surface K_V1.2α channels in transfected mammalian COS-1 cells. In contrast, calnexin coexpression showed no effect on trafficking of intracellularly retained K_V1.1 or K_V1.6α subunits³.

Calnexin has been implicated in the pathophysiology of cystic fibrosis disease (CF). Wild type and ΔF508 mutant cystic-fibrosis conductance regulator (CFTR) associate with calnexin in a Chinese hamster ovary (CHO) cell model. Although both wild-type and ΔF508 CFTRs are present in complexes with calnexin, only wild-type CFTR is able to escape this association and exit the ER. This suggests that calnexin retains misfolded proteins in the ER and contributes to the mislocalization of mutant CFTRs.