MBTPS1 (S1P) cleaves the lumenal domain of CREB3L4 (Stirling and O'Hare 2006, Ben-Aicha et al. 2007). Based on homology with SREBFs (SREBPs), other CREB3 proteins, and the mouse homolog Creb3l4 (Tisp40) the cleavage site is inferred to be at a RNIL motif at amino acid 338. The C-terminal domain of CREB3L4 interferes with cleavage and therefore may regulate the process (Stirling and O'Hare 2006). Dithiothreitol (DTT) causes trafficking but not cleavage of CREB3L4.