γ-Secertase is one of intramenbrane-cleaving aspartyl protease which cleaves many type-I membrane proteins and many of them have important biological functions. γ-Secretase is a multi-subunit protease and it contains presenilin, nicastrin, APH-1(Anterior Pharynx- defective 1) and PEN-2. Presenilin contains Asp258 and Asp385 embedded in the sixth and seventh transmembrane domain and forms the active site. The feature of being a membrane integrated protease complex makes it difficult to be purified as well as studying its mechanism.γ-secretase is responsible for the generation Aβfrom the amyloid precursor protein.γ-Secertase has been considered as an important drug target for Alzheimer's disease.γ-Secertase also is responsible for Notch processing which is related to cancer such as leukemia.