APH1 is a multipass transmembrane protein that interacts with presenilin (see PSEN1; MIM 104311) and nicastrin (APH2; MIM 605254) as a functional component of the gamma-secretase complex. The gamma-secretase complex is required for the intramembrane proteolysis of a number of membrane proteins, including the amyloid-beta precursor protein (APP; MIM 104760) and Notch (MIM 190198).