PEX5 is a soluble peroxisomal import receptor essential for protein translocation into peroxisomes. As a primary function, PEX5 mediates the import of folded cargo proteins containing PTS1-type targeting signals from the cytosol into peroxisomes 1. Mechanistically, PEX5 partitions selectively into a YG-domain rich phase formed by the peroxisomal membrane protein PEX13, which creates an aqueous conduit resembling nuclear pores through which PEX5 delivers cargo across the membrane 1. PEX5 undergoes ubiquitination on peroxisomes as part of quality control, with ubiquitinated PEX5 serving as a signal for selective peroxisomal autophagy (pexophagy) during cellular stress 234. During viral infections and amino acid starvation, PEX5 ubiquitination is promoted through ATM pathway activation, recruiting p62 to trigger pexophagy and peroxisome degradation 35. Mutations in PEX5 cause peroxisome biogenesis disorders including Peroxisome Biogenesis Disorder 2A/2B and Rhizomelic Chondrodysplasia Punctata 5, characterized by impaired peroxisomal protein import and accumulation of unimported proteins. PEX5 additionally regulates redox homeostasis by binding MGST1 to maintain glutathione-dependent antioxidant function 4. Clinically, PEX5 deficiency enhances cellular sensitivity to oxidative stress and ferroptosis, suggesting therapeutic potential in cancer treatment combined with radiotherapy 4.