NOTCH receptor precursors (Pre-NOTCH) traffic from the endoplasmic reticulum to the Golgi. Endoplasmic reticulum calcium ATPases are required for maintenance of high levels of calcium and positively regulate NOTCH trafficking, perhaps by ensuring proper NOTCH folding. Exit of NOTCH precursors from the endoplasmic reticulum is negatively regulated by SEL1L (Li et al. 2010, Sundaram et al. 1993), an endoplasmic reticulum membrane protein that is part of the ERAD (endoplasmic reticulum associated degradation) system, which performs quality control and triggers degradation of misfolded proteins (Francisco et al. 2010). NOTCH trafficking through the Golgi and trans-Golgi network is positively regulated by RAB6, a Golgi membrane GTPase.