Rethinking Complement in Homeostasis and Disease

The complement system, traditionally viewed as a central component of immune defense, is now recognized to play diverse roles in morphogenesis, tissue regeneration, cellular metabolism, and intercellular communication. This expanded perspective highlights the spatially distributed and context-dependent nature of complement activity. Consequently, our understanding of complement-mediated diseases has evolved from a model centered on excessive activation to one in which chronic inflammatory processes displace protective, complement-regulated homeostatic functions. In this review, we examine several diseases that exemplify this paradigm and discuss how this conceptual framework may inform the development of innovative therapeutic strategies aimed at restoring complement-mediated homeostasis.