As scientists, it's important for us to keep an open mind. Sometimes it might seem that there's little more to discover about a particular pathway or protein, but we will usually find that there's more to be uncovered. For example, on page 464, Stevan R. Hubbard discusses how the juxtamembrane region of receptor tyrosine kinases (RTKs) regulates their activity. RTK catalytic activity has been known for some time to be modulated by their kinase-activation segment, but recent studies have shown that the juxtamembrane region of several RTK subclasses also has a key role in kinase regulation.

And, on the subject of RTKs, Hong Joo Kim and Dafna Bar-Sagi review Sprouty — a recently identified repressor of RTK signalling in vertebrates and invertebrates — on page 441. Although it initially seemed that the antagonistic function of Sprouty could be easily explained, it is now becoming clear that its mode of action is multifaceted and is subject to complex regulation.

Moving away from RTKs, Raphael Kopan and Ma. Xenia G. Ilagan discuss a potential new role for γ-secretase on page 499. This intramembrane protease mediates signalling (for example, Notch signalling) by releasing the intracellular domains of receptors. However, many new γ-secretase substrates have recently been identified, which indicates a broader role for this protease. So, might this enzyme be the proteasome of the membrane?

Finally, it has long been known that organisms use protein-based control systems to modulate gene expression, but recent studies have shown that RNA is more extensively involved in fundamental gene-control processes than was previously assumed. On page 451, Maumita Mandal and Ronald R. Breaker discuss riboswitches — folded RNA domains that are found in the non-coding portions of various mRNAs and that function as metabolite-sensing gene regulators.