Pex5Pex7

PEX5PEX7 refers to the coordinated system of two peroxisomal import receptors, PEX5 and PEX7, that together mediate the delivery of matrix proteins to peroxisomes. PEX5 specializes in recognizing cargo proteins bearing a C-terminal peroxisomal targeting signal type 1 (PTS1), while PEX7 recognizes proteins with an N-terminal peroxisomal targeting signal type 2 (PTS2). In many animal cells, PEX5 can function as a co-receptor for PTS2-bearing proteins by forming a transient complex with PEX7, enabling import of these proteins through the same translocation machinery.

The import process begins in the cytosol, where PTS1 and PTS2 cargoes bind their respective receptors. The receptor–cargo complexes then dock at the peroxisomal membrane via a docking complex that includes proteins such as PEX13 and PEX14. After docking, the cargo is translocated into the peroxisomal matrix, and the receptors are recycled back to the cytosol, a process that involves ubiquitination and other peroxins to maintain import efficiency. In mammals, PEX5 long form (PEX5L) and the tail-anchored membrane protein PEX26 facilitate this docking and recycling, coordinating with PEX13/PEX14 to form a functional import pore.

Species differences exist in how PEX5 and PEX7 collaborate. In yeast, additional co-receptors such as Pex18 and Pex21 participate in PTS2 import, whereas in many animals the PEX5–PEX7 interaction is central for PTS2 cargo delivery.

Clinical relevance centers on peroxisomal biogenesis disorders. Mutations in PEX5 or PEX7 impair import of PTS1- and PTS2-containing proteins, leading to metabolic disturbances, abnormal plasmalogen synthesis, and accumulation of very-long-chain fatty acids, with presentations ranging from severe developmental disorders to milder phenotypes.