Not only membrane proteins surviving the first checkpoint are controlled for their luminal domains, also soluble proteins are inspected by this pathway as they are entirely luminal and thus bypass the first checkpoint. If a lesion in the luminal domains is detected, the involved protein is processed for ERAD using a set of factors including the vesicular trafficking machinery that transports misfolded proteins from the endoplasmic reticulum to the Golgi apparatus.
Proteins that survive the initial checkpoint are scrutinized for their luminal domains, and soluble proteins are also inspected by this pathway because they are entirely luminal and thus bypass the first checkpoint. If a defect is found in the luminal domain of a protein, it triggers ERAD, which involves vesicular trafficking machinery to transport misfolded proteins from the endoplasmic reticulum to the Golgi apparatus.