DOI: 10.1083/jcb.202610007 ISSN: 0021-9525

Swollen lysosomes grab Rabs for a CASM-free route to LRRK2 activation

Suzanne R. Pfeffer

Multiple lysosomal stresses activate Parkinson’s-linked LRRK2 kinase, and these involve the so-called “CASM” pathway to help recruit LRRK2 to lysosome surfaces. Clegg et al. (https://doi.org/10.1083/jcb.202511137) show that LRRK2, activated upon lysosome swelling caused by PIKfyve inhibition, instead relies solely on Rab GTPase binding for lysosome localization and activation.

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