A staggering 8% of the human genome derives from endogenous retroviruses, ancient evolutionary fossils that have been dismissed as vestiges. Yet recent work has revealed that some of these viral genes have been repurposed for essential functions in host biology, and in a twist of genetic irony, can even be co-opted to inhibit retroviral infection. My lab is poised to unveil the profound impact of these repurposed retroviral genes on human immunity. Leveraging our expertise in high-throughput functional virology and immunology, we will identify human endogenous retroviruses that either function as novel antiviral defenses, or engage with known antiviral immunity to alter its evolutionary trajectory. Our work will reveal how these ancient retroviruses have shaped the evolution of human immunity, influencing our susceptibility to viral pandemics like HIV. These findings will redefine ERVs from “junk DNA” to critical functional players of the human genome.