Frontotemporal lobar degeneration (FTLD), which underlies frontotemporal dementia (FTD), encompasses a group of disorders with significant genetic, clinical, and neuropathological heterogeneity. Dr. Petrucelli’s project aims to understand the molecular underpinnings of TAR DNA-binding protein 43 (TDP-43) localization and consequences of its dysfunction in disease. The group will investigate the mechanisms underlying cryptic splicing in TDP-43 proteinopathies, the role of cryptic RNA and proteins in FTLD, and the role of the endo-lysosomal system in the development of TDP-43 pathology and neurodegeneration. Dr. Petrucelli’s group will also explore the emerging role of Transmembrane Protein 106B (TMEM106B) fibrillogenesis in different neurodegenerative diseases, including TDP-43 proteinopathies and tauopathies.