Abstract: The present invention relates to a cellular screening method for the identification of modulators of secretases. Said method comprises contacting suitable host cells with a test substance wherein said suitable host cells comprise: a) a fusion protein secretory protein, a membrane anchor domain and a secrease cleavage sequence, b) a protein comprising a secretase activity recognising said cleavage sequence of said fusion protein and a) at least one reporter gene under control of a transcriptional activation system wherein said transcriptional activation system is regulated by the release of said secretory protein from said fusion protein by said secretase activity and its subsequent secretion then culturing said cells under suitable conditions such that said reporter gene allowing detection and/or survival of cells is only expressed or repressed in a manner that is dependent on an altered secretase activity due to said test substance.