Peroxisomal biogenesis factor 12 (PEX12)

Peroxisomal biogenesis factor 12 (PEX12) is an **integral membrane protein** of the peroxisome, crucial for peroxisome biogenesis and maintenance[1][3]. PEX12 is one of three RING finger domain-containing proteins (the others are PEX2 and PEX10) that form a ubiquitin ligase complex embedded in the peroxisomal membrane[2][4][5]. This complex acts as a **retrotranslocation channel for recycling peroxisomal import receptors**, notably **PEX5**, which must be exported from the peroxisome back to the cytosol after delivering their cargo[3][4][5]. \n\nPEX12 specifically facilitates the **monoubiquitination of PEX5 via the E2 enzyme PEX4**, enabling receptor recycling. If PEX5 recycling fails, PEX12 supports PEX10-mediated polyubiquitination of PEX5, directing it toward proteasomal degradation[2][3][5]. Mutations in PEX12 are genetic causes of **peroxisomal biogenesis disorders** (PBDs), most notably **Zellweger syndrome** and related disorders, characterized by profound impairment of peroxisomal function[1][3]. \n\nPEX12 is a **359 amino acid, ~41 kDa protein** with two transmembrane segments and cytoplasmic N- and C-termini. The N-terminal region mediates correct localization to the peroxisome, while the C-terminal region contains an atypical RING finger domain essential for ubiquitin ligase activity and interactions with protein partners (including PEX5, PEX10, PEX19). It is conserved among all eukaryotes harboring peroxisomes[1][3][5]. \n\nThere are currently no drugs directly targeting PEX12, and it is not recognized as a traditional therapeutic target such as a receptor, enzyme, or transporter. Instead, its primary clinical role lies in genetics and diagnostics for peroxisome biogenesis disorders[3].

Other names

Peroxisome assembly protein 12Peroxisome assembly factor 3Peroxin-12PAF3PAF-3PBD3APeroxin 12