Transposable elements (TEs) are a prolific source of regulatory elements and gene products, contributing to the regulation of host genes. Recent studies have reinvigorated the idea that TEs play a significant role in gene regulation. The authors argue that the genetic properties of TEs and their conflicting relationships with hosts facilitate their recruitment for regulatory functions. They review recent findings supporting the hypothesis that TE invasions have catalyzed the evolution of gene regulatory networks. The article discusses the challenges in interpreting the phenotypic impact of TE-derived regulatory activities in health and disease. TEs have evolved mechanisms to mimic host promoters and regulatory elements, leading to diverse regulatory contributions to organismal physiology and pathology. The authors highlight the need for responsible assignment of functional roles to TEs and propose future directions for research. They also discuss the potential pathogenic effects of TE regulatory activities, including their role in disease states such as cancer and neurological disorders. The article concludes by emphasizing the importance of understanding the long-term evolutionary implications of TE dispersal and the need for more direct assessments of their biological consequences.Transposable elements (TEs) are a prolific source of regulatory elements and gene products, contributing to the regulation of host genes. Recent studies have reinvigorated the idea that TEs play a significant role in gene regulation. The authors argue that the genetic properties of TEs and their conflicting relationships with hosts facilitate their recruitment for regulatory functions. They review recent findings supporting the hypothesis that TE invasions have catalyzed the evolution of gene regulatory networks. The article discusses the challenges in interpreting the phenotypic impact of TE-derived regulatory activities in health and disease. TEs have evolved mechanisms to mimic host promoters and regulatory elements, leading to diverse regulatory contributions to organismal physiology and pathology. The authors highlight the need for responsible assignment of functional roles to TEs and propose future directions for research. They also discuss the potential pathogenic effects of TE regulatory activities, including their role in disease states such as cancer and neurological disorders. The article concludes by emphasizing the importance of understanding the long-term evolutionary implications of TE dispersal and the need for more direct assessments of their biological consequences.