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Purifying and profiling lysosomes to expand understanding of lysosomal dysfunction–associated diseases
Ali Shilatifard, Issam Ben-Sahra
Ali Shilatifard, Issam Ben-Sahra
Published February 17, 2025
Citation Information: J Clin Invest. 2025;135(4):e188507. https://doi.org/10.1172/JCI188507.
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Purifying and profiling lysosomes to expand understanding of lysosomal dysfunction–associated diseases

Abstract

Lysosome storage dysfunction plays a central role in numerous human diseases, but a lack of appropriate tools has hindered lysosomal content profiling in clinical settings. In this issue of the JCI, Saarela et al. introduce a method called tagless LysoIP that enabled rapid isolation of intact lysosomes from blood and brain cells via immunoprecipitation of the endogenous protein TMEM192. Applied to the neurodegenerative lysosomal storage disorder known as Batten disease (caused by mutations in the CLN3 gene), tagless LysoIP revealed substantial accumulation of glycerophosphodiesters (GPDs) in patient lysosomes. These findings highlight the role of CLN3 in GPD clearance and present an innovative method that will enable biomarker discovery and therapeutic advancement in lysosomal diseases.

Authors

Ali Shilatifard, Issam Ben-Sahra

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