Genetics leads the way to the accomplices of presenilins.

Presenilins mediate the γ-secretase cleavage of Notch transmembrane receptors as well as the transmembrane β-amyloid precursor protein (βAPP), but they are not thought to accomplish this alone. Recent genetic screens in C. elegans, presented in this issue of Developmental Cell, identify two genes that are essential to γ-secretase activity and may interact with presenilins.