PEX7s

PEX7s are peroxisomal protein import receptors that recognize proteins bearing the peroxisomal targeting signal type 2 (PTS2) and mediate their import into the peroxisomal matrix. They function in the cytosol and, upon binding a PTS2-containing cargo, interact with the peroxisomal membrane docking system to deliver the cargo into the organelle.

In many organisms, PEX7 works with co-receptors or accessory factors to stabilize the cargo-receptor complex and enable docking at the peroxisomal membrane. The exact set of co-factors varies by species, and the docking platform typically involves core peroxins such as PEX13 and PEX14. After translocation into the peroxisome, the cargo is processed as needed, and the PEX7 receptor is recycled back to the cytosol by an ATP-dependent import motor and associated ubiquitination factors, allowing repeated rounds of import.

PEX7 genes are found across a wide range of eukaryotes, reflecting the conservation of the PTS2 pathway. However, the reliance on PTS2 import varies, and some lineages emphasize the PTS1 pathway or possess only a partial PTS2 system. In these organisms, PEX7 may be absent or functionally modified, illustrating the evolutionary flexibility of peroxisomal protein targeting.

Clinical relevance in humans centers on PEX7’s role in importing PTS2-containing enzymes. Mutations that disrupt PEX7 function cause Rhizomelic chondrodysplasia punctata type 1 (RCDP1), a peroxisomal biogenesis disorder characterized by skeletal abnormalities, cataracts, neurologic impairment, and reduced life expectancy. The condition highlights the importance of the PTS2 import pathway for peroxisome function and organismal development.