Presenilin: RIP and beyond. Left: γ-secretase-dependent functions of presenilin (PSEN). PSEN/γ-secretase modulates cellular signaling pathways through RIP. Asterisks indicate target genes that are under debate as discussed in the text. PSEN/γ-secretase may also function as a proteasome. Right: Other emerging functions of PSEN. PSEN is also implicated in Wnt signaling, cell adhesion, trafficking, calcium regulation and apoptosis. See the corresponding sections for detail. AbbreviationsAβ; amyloid β peptide, AICD; APP intracellular domain, APP; Amyloid β precursor protein, ErbB4ICD; ErbB4 intracellular domain, Nct; Nicastrin, NICD; Notch intracellular domain, RIP; regulated intramembrane proteolysis, SERCA; sarcoplasmic ER Ca2+ ATPase.