Hippo activation appears to require the participation of multiple scaffolds that assemble multi-protein complexes. A) In Drosophila, both Sav and Ex can interact with both Hpo and Wts. B) Ex is partially redundant with Merlin and Kibra (depending upon the tissue), which can interact with Wts and Sav. C) In mammals, Merlin (NF2) and Motins play key roles in Hippo pathway activation. Merlin and Kibra can each interact with SAV1 and LATS, and Motins can interact with LATS, Merlin, and Kibra.