PEX5L (peroxisomal biogenesis factor 5 like) is the long isoform of PEX5, functioning as a critical receptor for peroxisomal protein import. As a cytosolic receptor, PEX5L recognizes and binds peroxisomal matrix proteins carrying peroxisomal targeting signals, particularly PTS2-targeted proteins, which distinguishes it from the shorter PEX5S isoform 1. Upon cargo binding, PEX5L is recruited to peroxisomal membranes where it interacts with the docking protein PEX14 and becomes integrated into the peroxisomal translocon complex 2. Mechanistically, PEX5L forms the pore-forming component of the oligomeric peroxisomal translocon, with membrane-bound PEX5L capable of forming ion-conducting channels that facilitate substrate translocation into the peroxisomal matrix 3, 2. Loss of PEX5L specifically causes rhizomelic chondrodysplasia punctata type 5 (RCDP5), characterized by selective deficiency in PTS2 protein import 4. Beyond peroxisomal function, PEX5L expression levels show prognostic significance in non-small cell lung cancer, with high expression associated with worse survival 5, and it contributes to a peroxisomal metabolic signature in colorectal cancer progression 6. Recent evidence indicates SARS-CoV-2 infection suppresses PEX5L expression in the central nervous system, potentially contributing to neurological complications of COVID-19 7.