Following initial synthesis and membrane integration (step 1), nascent CFTR molecules are inefficiently folded (step 2) and are recognized as misfolded by one or more components of the quality control machinery (red; step 3a), which may interact with cytoplasmic, membrane, or lumenal portions of CFTR. This interaction is necessary to dislocate CFTR to the cytoplasmic ubiquitin (green spheres) conjugation machinery (step 3b), which then directs it to the proteasome for degradation (step 3c). Cytoplasmic aggregates form (step 3d) when the rate of production and dislocation of misfolded CFTR exceeds the capacity of the ubiquitin-proteasome system for degradation.