Here, we assessed whether a brain penetrant SCD inhibitor, 5b, can prevent the PD-like neuropathology in GBA1 mutant neuronal culture and in 2 Gba1 mutant mouse lines, expressing either the more common and severe L444P mutation or the E326K mutation—both risk factors for the development of PD (74, 75). Here, SCD is linked to Parkinson disease.