Two small‑molecule programs aimed at activating glucocerebrosidase (GCase) in Parkinson’s disease reported early signals of target engagement. Gain reported substrate reduction in the CNS for its candidate, while Vanqua disclosed peripheral enzyme activation plus evidence of CNS penetration. Both companies published preliminary biomarker and pharmacodynamic readouts that suggest modulation of GCase biology is achievable with small molecules. The data are early and not yet tied to clinical outcomes, but they add mechanistic validation to GCase as a target for synucleinopathy treatment. Sponsors will need to demonstrate durable biochemical effects, clinical benefit on motor and nonmotor symptoms, and acceptable safety to move these programs forward in Parkinson’s, a field with urgent need for disease‑modifying therapies.