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Despite their recent identification, TDases have rapidly disseminated worldwide, largely driven by mobile genetic elements and environmental reservoirs. This review synthesizes current knowledge on TDase genomics, structural and catalytic mechanisms, ecological niches, and clinical impacts. We detail the mechanistic distinctions between type 1 and type 2 TDases, emphasizing their divergent structural configurations and substrate specificity profiles. Additionally, we examine strategies for therapeutic intervention, highlighting progress in structure\u2010guided inhibitor development. Key gaps remain in understanding ancestral reservoirs, evolutionary trajectories, and effective surveillance strategies. 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