Toxins in disguise: Neuropeptide mimicry across animal venoms

• Many venomous animals have evolved doppelgänger toxins that mimic these endogenous peptides. • Doppelgänger toxins allowing venomous animals to manipulate the physiology of their target. • Doppelgänger toxins have potential in drug development and as biopesticides. • Here, we catalogue known examples of doppelgänger toxins from venomous animals. Neuropeptides and peptide hormones form a highly diverse class of signaling molecules found across the animal kingdom that regulate key physiological processes, including growth, metabolism, reproduction, and behavior. Many venomous animals have evolved “doppelgänger toxins” that mimic these endogenous peptides, allowing them to manipulate the physiology of their prey or predators. These toxins typically act on the same receptors as the peptides they mimic, most commonly G protein-coupled receptors, but also receptor tyrosine kinases, membrane-bound guanylyl cyclases, and ion channels. Although doppelgänger peptides have been described in other ecological contexts, this review focuses on venom-derived mimics, summarizing their molecular characteristics, evolutionary context, and biological functions. We catalogue examples spanning conserved bilaterian neuropeptides to lineage-specific families and discuss their translational potential in medicine and pest control.