Parkinson’s disease (PD) is a neurodegenerative disorder that causes debilitating motor impairment. But it is also often preceded by intestinal issues, suggesting that the gut may play a role in PD development. Researchers have been trying to unravel the causes of PD and the role of the gut-brain axis, and the humble fruit fly, Drosophila, is helping them do it. Fruit flies with a mutated pink1 gene have dopaminergic neuron breakdown and gut dysfunction, just like humans with PD, and PINK1 mutations in people cause early-onset PD. The mutant flies also lack critical proteins due to sustained activation of dPerk, an enzyme that activates the unfolded protein response (UPR), which is another feature of PD. A recent study in the fruit flies found that intestinal expression of dPerk impairs mitochondrial function, causes cell death, and decreases lifespan. Suppressing dPerk expression in the intestine reduced cell death and protected the brains of pink1 mutants from degeneration, suggesting that blocking transmission of UPR-related toxicity from the gut to the brain can be neuroprotective. These results in fruit flies with pink1 mutations highlight the importance of the gut-brain axis in PD and could lead to new insights into this awful disease.