Peroxin 5R Activators

Peroxin 5R, typically referred to as PEX5R or PEX5-related protein, is a paralog of the PEX5 protein which is a key component of the peroxisomal protein import machinery in humans. The peroxisome is a single-membrane-bound organelle present in virtually all eukaryotic cells, involved in various metabolic pathways including the beta-oxidation of very long-chain fatty acids, the metabolism of hydrogen peroxide via catalase, and the biosynthesis of plasmalogens, which are essential components of myelin in nerve cells.PEX5R is homologous to the canonical PEX5 and binds to peroxisomal targeting signal 1 (PTS1)-containing proteins in the cytosol, functioning as their receptor. Once bound to its cargo proteins, the PEX5R-cargo complex interacts with docking proteins at the peroxisomal membrane, facilitating the translocation of these proteins into the peroxisome. Unlike PEX5, PEX5R does not usually bind to PTS2-containing proteins.

The importance of PEX5R lies in its role in human health and disease. Mutations in the gene encoding PEX5R can lead to peroxisomal biogenesis disorders (PBDs), a group of inherited metabolic disorders that result from the dysfunction of peroxisomes. These disorders often present with severe developmental, neurological, and hepatic abnormalities, underscoring the significance of peroxisomal function in human physiology.PEX5R is also implicated in the regulation of peroxisome size, number, and distribution within cells. Its interaction with the peroxisomal membrane and the subsequent recycling back to the cytosol is a tightly regulated process, indicative of the elaborate control mechanisms that govern peroxisomal protein import.