The article reviews the recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE), which is characterized by a stereotypical TDP-43 proteinopathy in older adults, often associated with hippocampal sclerosis. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology by its epidemiology and neuroanatomical distribution of TDP-43 proteinopathy. Community-based autopsy studies show that approximately 25% of brains have sufficient LATE neuropathological changes (LATE-NC) to be associated with cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, including amyloid-β plaques and tauopathy. Given the increasing prevalence of advanced age, LATE has an expanding but under-recognized impact on public health. The article proposes new terminology and diagnostic criteria for LATE, including guidelines for diagnosis and staging of LATE-NC. It also highlights the need for specific biomarkers and targeted therapies to address the growing burden of LATE.The article reviews the recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE), which is characterized by a stereotypical TDP-43 proteinopathy in older adults, often associated with hippocampal sclerosis. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology by its epidemiology and neuroanatomical distribution of TDP-43 proteinopathy. Community-based autopsy studies show that approximately 25% of brains have sufficient LATE neuropathological changes (LATE-NC) to be associated with cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, including amyloid-β plaques and tauopathy. Given the increasing prevalence of advanced age, LATE has an expanding but under-recognized impact on public health. The article proposes new terminology and diagnostic criteria for LATE, including guidelines for diagnosis and staging of LATE-NC. It also highlights the need for specific biomarkers and targeted therapies to address the growing burden of LATE.