Complement in motion: The evolution of CD46 from a complement regulator to an orchestrator of normal cell physiology

The classic pathogen-fighting functions of our microbe sensing systems, such as the TLRs, the Nod-like receptors, and several proteins of the complement system, had been defined relatively rapidly after their discovery (1, 2). A more recent trend, however, clearly indicates that some of these evolutionarily ancient systems also serve additional, noncanonical roles in normal cell physiology. In this article, we highlight how the functions of the complement component CD46 have expanded dramatically beyond its initial discovery as a regulator of complement activation. We now recognize this ancient molecule as a biological focal point for our continuously evolving understanding of the diverse roles of complement as a key orchestrator of (immunological) health.

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