PEX16 is an integral endoplasmic reticulum (ER) membrane protein essential for peroxisomal biogenesis. Functionally, PEX16 acts as a receptor that recruits peroxisomal membrane proteins, particularly PEX3 and PMP34, to nascent peroxisomes derived from the ER 1. In mammalian cells, newly synthesized peroxisomes arise from hybrid mitochondrial and ER-derived pre-peroxisomes; PEX16-containing ER vesicles fuse with mitochondria-derived pre-peroxosomes carrying PEX3 and PEX14 to generate fully competent organelles 2. Recently, PEX16 was shown to regulate peroxisomal-mitochondrial communication through plasmalogen synthesis; adipose-specific Pex16 knockout impaired cold-induced thermogenesis by disrupting mitochondrial fission and reducing plasmalogen abundance 3. PEX16 mutations cause peroxisome biogenesis disorder (PBD), an autosomal recessive disease with highly variable severity 4. Patients present a broad clinical spectrum from severe Zellweger syndrome with neurological dysfunction and early death to atypical PBD with mild biochemical disruptions and long survival 5. Interestingly, PEX16 knockout cells retain residual peroxisomal capacity, suggesting PEX16 accelerates rather than absolutely requires peroxisome formation 6. PEX16 physically interacts with PEX3 at the ER-peroxisomal interface 7, establishing its critical role in membrane protein targeting and organelle assembly.