The article "Disentangling Tau: One Protein, Many Therapeutic Approaches" by Courtney Lane-Donovan and Adam L. Boxer reviews the current state of tauopathies, a group of neurodegenerative diseases characterized by the accumulation of insoluble tau protein. Despite years of drug development, no therapeutic directed against tau has been approved for clinical use. The authors highlight the complex biology and genetics of tau, including its various isoforms, post-translational modifications, and the role of genetic mutations in tauopathies. They discuss the challenges in therapeutic development, such as the lack of precision in identifying patients early in the disease course and the variability in clinical phenotypes and underlying pathology. The article also reviews current and failed clinical trials, emphasizing the need for better biomarkers, more diverse patient populations, and innovative trial designs. Finally, the authors offer suggestions for new pathways in therapeutic development, expressing optimism for the future of tau-related treatments.The article "Disentangling Tau: One Protein, Many Therapeutic Approaches" by Courtney Lane-Donovan and Adam L. Boxer reviews the current state of tauopathies, a group of neurodegenerative diseases characterized by the accumulation of insoluble tau protein. Despite years of drug development, no therapeutic directed against tau has been approved for clinical use. The authors highlight the complex biology and genetics of tau, including its various isoforms, post-translational modifications, and the role of genetic mutations in tauopathies. They discuss the challenges in therapeutic development, such as the lack of precision in identifying patients early in the disease course and the variability in clinical phenotypes and underlying pathology. The article also reviews current and failed clinical trials, emphasizing the need for better biomarkers, more diverse patient populations, and innovative trial designs. Finally, the authors offer suggestions for new pathways in therapeutic development, expressing optimism for the future of tau-related treatments.