Does LRRK2's role as a lysosomal volume sensor explain the pathogenic mechanism of disease-linked LRRK2 mutations?

Analysis ID: SDA-2026-04-16-gap-pubmed-20260410-170027-a1e5f867 | Domain: neurodegeneration | Status: completed | Created: 2026-04-16T09:45:00.447078

Top Hypotheses (1 total)

#1 LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation via SIRT1/PGC1α Suppression

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Disease-linked LRRK2 mutations (G2019S, R1441C) cause excessive Rab phosphorylation during lysosomal swelling, creating a persistent 'volume sensing ON' state that chronically activates LRRK2 kinase.

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