The National Institute on Aging awarded Case Western Reserve University $1,785,220 under the Aging Research program (CFDA 93.866) from May 2022 to April 2025. The university will research the role of deubiquitinase USP19 in the pathogenesis of TDP-43, a protein implicated in neurodegenerative diseases like frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Using mouse models, human post-mortem tissues, and molecular and cell biology techniques, the university aims to validate USP19's role in vivo, and determine the mechanism by which it regulates TDP-43 stability, aggregation, and toxicity. Insights into USP19's deubiquitinating activity and interaction with TDP-43 could provide a potential therapeutic target to mitigate TDP-43 pathology and toxicity. The grant will support research toward understanding the aging process and diseases affecting older populations.