PEX12 is a peroxisomal membrane protein that forms part of a retrotranslocation channel essential for peroxisomal protein import. As a component of a multi-subunit ubiquitin ligase complex alongside PEX2 and PEX10, PEX12 mediates the recycling of PEX5, the primary import receptor for peroxisomal matrix proteins 1. The protein contains two transmembrane segments and a zinc-binding RING domain that enable its interaction with PEX5 and PEX10; once PEX5 delivers cargo into the peroxisomal lumen, PEX12 regulates its monoubiquitylation and extraction back to the cytosol for reuse. If recycling is impaired, PEX12 activates PEX10-mediated polyubiquitylation of PEX5, leading to its proteasomal degradation. Biallelic PEX12 mutations cause peroxisomal biogenesis disorders (PBDs), a group of genetically heterogeneous diseases including Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease 2. The severity of clinical and cellular phenotypes correlates with PEX12 mutation type; truncating mutations that eliminate the zinc-binding domain cause more severe presentations, whereas missense mutations or those permitting downstream translation initiation associate with milder phenotypes 3. At the population level, gnomAD v4.1 classifies PEX12 as loss-of-function tolerant (LOEUF=1.22); this is distinct from clinical pathogenicity observed in peroxisomal biogenesis disorder contexts, where 118 pathogenic variants are catalogued in ClinVar.