Retrotransposons unplugged: Rewiring the nervous system and wreaking havoc

The retrotransposons and endogenous retroviruses (ERVs) that contain long terminal repeat (LTR) sequences are a subset of transposable elements (TEs) that make up around 8% of the human genome. These retroelements (retroTEs) are derived from ancient retroviral infections or retrotransposons that have become permanently integrated into the germline and include domesticated retroTEs, such as the neuronal gene Arc. Until recently, limited tools and difficulties in mapping retroTEs have made it challenging to study these elements in detail. However, recent advances have revealed that retroTEs play a role in both human disease and physiological processes in the brain. Here, we highlight studies showing that retroTE nucleic acid and protein products perform unique functions in intercellular signaling and nervous system dysfunction. We discuss how these elements play critical roles in complex processes such as cognition and how future work will provide insight into neurological disorders.