Calnexin is a type I endoplasmic reticulum integral membrane Phorbol 12,13-dibutyrate protein with a single transmembrane helix followed by a cytoplasmic negatively charged Pristimerin C-terminal tail. The ER luminal domain of calnexin is responsible for lectin-like activity and interaction with nascent polypeptide chains. Calnexin, together with calreticulin, constitute the calnexin/calreticulin cycle responsible for the folding and quality control of newly-synthesized proteins. Calnexin has also been implicated in influencing Ca2+ regulation, cell-cell adhesion, phagocytosis, and cell sensitivity to apoptosis. X-ray crystallography studies have identified the ER luminal domain of calnexin as forming a globular b-sandwich containing a glucose binding site with a proline-rich portion of the protein forming an extended arm structure, a docking site for oxidoreductase ERp57. The C-terminal portion of calnexin extends 86 amino acid residues but its significance to calnexin function is not clear. This C-terminal domain of calnexin undergoes protein kinase-dependent phosphorylation and this modification may play a role in the chaperon function of the protein. Endocytosis is a process by which cells internalize materials into the cell by engulfing them with plasma membrane. One sub-type of endocytosis, clathrin-dependent endocytosis, is responsible for the internalization of specific molecules into the cell including: pathogens, nutrients, antigens, growth factors and receptors. During clathrin-dependent endocytosis, molecules are taken into the cell by specific receptor-ligand interactions. Integral membrane proteins bind to cytosolic adaptors, which form a link to the cytoplasmic clathrin lattice. Accessory proteins, such as Eps15 and AP180, have the ability to affect the process of clathrin mediated endocytosis by facilitating the assembly of clathrin-coated pits. Although single-cell organisms use endocytosis as the means to obtain nourishment, higher organisms have adapted endocytosis for specialized functions. These functions include modulating interactions between signaling molecules and their receptors and providing a localized environment where signaling takes place. Endocytosis is especially vital for the neuronal system. These processes allows retrieved fused vesicles to refill the vesicle pool allowing sustained synaptic transmission and maintenance of terminal nerve size ; specific substances to cross the blood-brain barrier and enter the central nervous system ; and internalizes receptor-ligand complexes to nerve terminals for their intracellular signaling. Recent studies indicate that Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1 may play a role in modulation of endocytotic activity in neuronal cells.