YAP needs Nemo to guide a Hippo.

The Hippo growth control pathway coordinates cell proliferation, death, differentiation and stemness through regulatory phosphorylation of the YAP proto-oncoprotein, a major nuclear effector of Hippo signalling. In particular, YAP phosphorylation on Ser127 can promote inhibitory 14-3-3 interactions and cytoplasmic sequestration. Two studies in this issue of EMBO Reports show that Ser128 phosphorylation of YAP by the Nemo-like kinase (NLK) disrupts 14-3-3 interactions, thereby promoting nuclear accumulation of active YAP [1,2]. Notably, Ser127-phosphorylated YAP can be nuclear and co-transcriptionally active upon osmotic stress, thus, challenging the dogma of YAP regulation by Ser127 phosphorylation.