The emergence of metazoa involved the invention of new proteins to control cells as they were integrated into specialised tissues. These proteins established patterns of cellular organization including polarity in layers of cells. They also established controls on cell proliferation. Two related protein families, the ERM proteins (ezrin, radixin and moesin) and tumour suppressor NF2 or merlin, evolved near the origin of metazoa. The ERM proteins are involved in coupling membranes to the actin cytoskeleton and play a role in apical-basolateral cell polarity. Merlin is also localised to the cell membrane and interacts with actin, however, it also acts in the cell nucleus controlling contact inhibition of cell proliferation. The proteins in these two families share a common architecture: an N-terminal FERM domain, an intermediate helical coiled coil domain and a C-terminal actin-binding domain. All members share a high level of sequence identity (>70% between any two human ERMs and >40% between any human ERM and human merlin). The structures appear to be very similar. During metazoan evolution, most organisms appear to have a single merlin gene. In contrast, most invertebrates have a single ERM, while vertebrates have three paralogues: ezrin, radixin and moesin. We are examining the evolution and conservation of sequence and structural traits in the ERM/merlin family to understand how these proteins function in cells and to what level they interact with each other.