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Cathelicidins\u2014a family of antimicrobial peptides expanded in the genomes of marsupials\u2014are highly expressed in developing neutrophils. Sugar glider cathelicidins reside in two genomic clusters, and their coordinated expression is achieved by enhancer sharing within clusters and long-range physical interactions between clusters. Functionally, cathelicidins modulate immune responses and have potent antibacterial effects, sufficient to provide protection in a mouse model of sepsis. Evolutionarily, cathelicidins have a complex history, with marsupials and monotremes uniquely retaining both clusters among tetrapods. 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