HtrA1 is a member of the HtrA serine protease family, which is found ubiquitously in microbes, plants and animals. In humans, HtrA1 is upregulated in articular chondrocytes during arteroarthritis and is a tumour suppressor gene that is downregulated in highly invasive tumours. Homology between the N-terminal region of HtrA1 and follistatin (a Tgfβ antagonist) prompted Oka and co-workers (p. 1041) to examine whether HtrA1 contributes to these diseases by inhibiting Tgfβ signalling. They found that HtrA1 binds to a broad range of Tgfβ family proteins. Furthermore, HtrA1 expression correlates with Tgfβ activity during mouse development, and misexpression of HtrA1 near to the chick eye suppresses eye development. Surprisingly, however, the inhibition of Tgfβ signalling by HtrA1 requires HtrA1 proteolytic activity, leading the researchers to propose that the binding of HtrA1 to Tgfβ may not itself inhibit Tgfβ, but may help degrade component(s)of Tgfβ signaling by bringing HtrA1 close to its substrate.