MAPT and proteostasis deficiencies: Pathological tau predominantly comprises 4-repeat (4R) isoforms, with ultrastructural features resembling both paired helical and ribbon-like filaments.4 Importantly, co-pathologies typically seen in other neurodegenerative diseases, including amyloid-deposit, α-synuclein, and TDP-43 positive inclusions, have not been observed.20 This absence suggests that SLC9A6-related disorders may predominantly involve tau pathology without evidence of additional proteinopathies.4