Nicastrin (NCT) is a 150 - 160 kDa member of the nicastrin family of proteins. It is a component of the aspartyl protease γ-secretase complex and serves to stabilize and direct γ-secretase components to proper positions in the plasma membrane. The γ-secretase complex mediates the cleavage of intramembrane proteins such as notch-1 and APP. Mature human nicastrin is a 676 amino acid type I transmembrane glycoprotein. It contains a 636 aa extracellular domain (aa 34 - 669) that shows a 58 aa sequence (aa 312 - 369) which interacts with γ-secretase substrates. There are multiple splice variants of nicastrin. Over aa 34 - 669, human nicastrin shares 90% aa identity with mouse nicastrin.