(A) Intralumenal proteostasis involves proteases and chaperones. Proteases cleave the PTS2 (peroxisome targeting signal 2) peptide and degrade damaged and obsolete proteins; chaperones assist protein folding, complex assembly, and aggregate dissociation. Peroxisomal proteins with cytosolic domains (e.g., PEX5) can be polyubiquitinated by a ubiquitin (Ub)-conjugating enzyme (PEX4) and the Ub-protein ligase complex (PEX2, PEX10, and PEX12) at the peroxisome membrane. (B) Polyubiquitinated proteins are degraded by the cytosolic 26S proteosome.