(A) Nuclear encoded peroxisomal protein genes are governed by various transcriptional activators (mauve) and repressors (teal) and are modulated during development and by abiotic and biotic challenges that elicit individual-protein and whole-organelle changes. (B) As part of the endomembrane system, peroxisomes arise from the ER as pre-peroxisomes lacking lumenal proteins. (C) mRNA of some peroxisomal membrane proteins (PMPs) are likely translated by ER-localized ribosomes and the protein is trafficked through the ER to bud with pre-peroxisomes. Other PMPs are translated by cytosolic and potentially peroxisome-localized ribosomes. PEX19 acts as a chaperone, binding to the mPTS (membrane peroxisome targeting signal) of PMPs and transferring mPTS-cargo to PEX3 for membrane insertion. (D) Mature peroxisomes contain PMPs, intralumenal vesicles (ILVs) derived from the outer membrane, and lumenal proteins. PTS1 and PTS2 (peroxisome targeting signal 1 and 2) cargo (enzymes, chaperones, proteases) are imported into the lumen via receptors (PEX5 and PEX7) and the membrane docking complex (PEX13 and PEX14). After delivery of lumenal cargo, PEX5 is monoubiquitinated by peroxisome-associated ubiquitination machinery (the PEX4-PEX22 ubiquitin conjugating enzyme complex and the PEX2-PEX10-PEX12 ubiquitin ligase enzyme complex) and retrotranslocated for reuse by an ATPase complex (PEX1, PEX6, and PEX26).