Zhenrun J Zhang, Yifat Merbl, Cesar de la Fuente-Nunez
Computational and experimental advances have led to the discovery of a large and diverse repertoire of bioactive peptides encrypted within proteins from across the tree of life. Mounting evidence suggests that these peptides can contribute to host defense not only through direct antimicrobial activity, but also through immunomodulatory and potentially broader physiological functions. This Essay synthesizes this emerging field from a broader biological perspective and explains the conceptual logic of immunity mediated by encrypted peptides. It proposes that such 'encrypted immunity' represents a previously underappreciated layer of host defense and physiology, with potential implications for therapeutics, diagnostics, and fundamental biology.