The cleavage process of sterol regulatory element binding proteins (SREBPs) shares several characteristics with that of β-amyloid precursor protein (βAPP). We studied the secretion of amyloid β protein Aβ from mutant M19 Chinese hamster ovary (CHO) cells that are defective in the site 2 cleavage of SREBPs. The levels as well as the C-terminal properties of Aβ secreted from M19 cells were similar to those from wild-type CHO cells, demonstrating that γ-cleavage of βAPP occurs normally in M19 cells. The present data indicated that γ-secretase of βAPP and SREBP site 2 protease are distinct enzymes.