This $393,750 Project Grant award from the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training program (CFDA 93.859) supports research at The Ohio State University focused on understanding lysosomal membrane dynamics under stress conditions. The project aims to elucidate the role of a recently identified cellular process called "lysosomal tubulation and sorting driven by LRRK2 (LYTL)" in maintaining cellular homeostasis, as well as examine a novel response to lysosomal membrane damage driven by certain annexin proteins. Additionally, the research will investigate how disease-relevant cell types, specifically human macrophages, respond to lysosomal membrane damage. The 5-year project is expected to provide new mechanistic insights into lysosomal quality control pathways and their potential therapeutic applications.