Cell membranes and trafficking disorders

Cell membranes are still a frontier in biochemistry. In fact, many aspects of cell membranes are still being explored today. The functions of cell membranes go beyond simply enclosing and compartmentalizing cells and organelles; it is now known that cell membranes regulate transport in and out of the cell, provide sites for enzyme binding and catalysis, direct cell organelle function, anchor filaments, etc. The complexity of cell membranes means that most diseases will involve its function in some way.

Cell membrane diseases can be classified in many different categories. Of those, a particularly important one is a disruption of membrane trafficking. Conservative estimates indicate that 10% of all cellular proteins are used in membrane trafficking.

Niemann-Pick disease type C (NPC) is a rare and intriguing disease that is currently being studied. NPC is a lysosomal storage disorder, which lacks an enzyme that allows normal operation of the cell’s recycling function. This can lead to harmful materials being stored inside the cell, leading to a deterioration of the cell. Specifically, NPC causes a lysosomal accumulation of LDL-derived cholesterol. Recent research has linked NPC to a malfunction of the NPC1L1 protein. This particular protein plays a role in the trafficking of intracellular cholesterol in the small intestine. The drug ezetimibe is used to treat this particular disease.

Interestingly, ezetimibe’s target protein was uncertain when the drug first hit the market. Only recently has the specific target of ezetimibe been determined to be NPC1L1. As scientists learn more about the complexities of the cell membrane, our knowledge of how to treat diseases becomes more comprehensive and sophisticated.