PEX3 is a peroxisomal membrane protein essential for peroxisome biogenesis and organelle integrity. As a docking factor for PEX19, PEX3 facilitates the import of peroxisomal membrane proteins by assembling membrane vesicles before matrix protein translocation 1. PEX3 functions in a hybrid biogenesis pathway where it initially targets mitochondria, is released into vesicular pre-peroxisomal structures, and subsequently fuses with endoplasmic reticulum-derived vesicles containing PEX16 to achieve full import competence 2. Beyond classical peroxisome biogenesis, PEX3 regulates cellular metabolism through plasmalogen synthesis, activating the AKT/GSK3Ξ² signaling pathway via ITGB3 plasma membrane localization to promote myocardial regenerative repair 3. PEX3 also functions in metabolic adaptation; melanoma cells utilize peroxisome biogenesis mediated by PEX3 to reprogram lipid metabolism and tolerate MAPK inhibitors, and PEX3 repression sensitizes melanomas to therapy 4. Pathologically, elevated Scpep1 binds PEX3 to promote its degradation, impairing mitochondrial bioenergetics and exacerbating myocardial infarction-induced cardiac dysfunction 5. PEX3 dysfunction is associated with peroxisome biogenesis disorders 10A/10B and complementation group 12, highlighting its critical clinical significance in human genetic disease.