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Endogenous retroviruses (ERVs) are heritable sequences in the genomes of animals and some plants that originate from ancient retroviral infections of germ cells. When a retrovirus integrates into a germline genome and that lineage is passed to offspring, the viral sequence becomes endogenous. Over evolutionary time, most ERVs accumulate mutations and become nonfunctional, leaving behind fragments or solo long terminal repeats (LTRs). In humans, ERV-derived sequences account for about 8% of the genome. Their typical architecture mirrors their ancestral retroviruses, with LTRs flanking internal genes such as gag, pol, and env, though many elements are highly degraded.

Many ERVs are domesticated or repurposed by the host. In mammals, certain env-derived genes, such as syncytin-1 and syncytin-2, have been co-opted to facilitate placental development by promoting cell fusion in the placenta. Beyond such domestication, ERV LTRs and other elements can act as regulatory sequences, influencing the expression of nearby genes during development and in immune responses.

In human health and disease, ERV activity is usually tightly controlled by epigenetic mechanisms, but reactivation can occur under certain conditions and has been associated with some cancers and autoimmune disorders. ERV proteins can be immunogenic, and ERV-derived sequences are studied as potential biomarkers or therapeutic targets. ERVs also serve as useful phylogenetic markers, helping researchers trace evolutionary relationships among species. Research on ERVs combines genomics, transcriptomics, and proteomics to understand their biology, evolution, and impact on host genomes.