Resolve: G2019S primarily raises baseline LRRK2 kinase activity rather than amplifying lysosomal swelling gain

Challenge generated from hypothesis h-d4ac0303f6 (composite_score=0.790). Target gene/pathway: LRRK2. Source hypothesis: G2019S primarily raises baseline LRRK2 kinase activity rather than amplifying lysosomal swelling gain. ## Falsifiable Predictions 1. G2019S-expressing cells show >2-fold elevation in basal pRAB10/total RAB10 (ELISA or proximity ligation assay) vs WT under normal culture conditions. 2. Lysosomal osmotic stress (ML-SA1, vacuolin-1) produces <30% additional pRAB10 increase in G2019S vs >60% in WT, confirming blunted dynamic range. 3. Partial LRRK2 inhibitor (MLi-2 at 10 nM, targeting basal not stress-peak kinase) normalises basal pRAB10 by >50% while preserving >70% of lysosomal stress-response signalling capacity. 4. Partial inhibition (basal-normalising dose) protects dopaminergic neurons in G2019S LRRK2 BAC mouse model (>80% TH+ neuron preservation vs vehicle) with no lysosomal swelling side-effects.