Abstract: A key pathological feature of Parkinson’s disease (PD) is that lysosomes are overwhelmed with cellular materials that need to be degraded and cleared. While the build-up of protein is characteristic of neurodegenerative diseases such as PD and Alzheimer’s disease (AD) and is thought to reflect lysosome dysfunction, lipid accumulation may also contribute to and be indicative of severe lysosomal dysfunction. Much is known about the detrimental effects of glucosylceramide accumulation in PD lysosomes. In fact, the most common genetic risk factor for PD is GBA1, which converts glucosylceramide to ceramide. Gaucher’s disease, which has a genetic overlap with PD, is a classic example of the toxic build-up of lysosomal lipids being associated with a neurodegenerative condition. The removal of diverse lipids, including sterols and sphingolipids from lysosomes and cells, occurs through the actions of a group of proteins known as ATP Binding Cassette subfamily A (ABCA) transporters (Lok et al., 2024). Results from a genome-wide association study indicate that ABCA5 single nucleotide polymorphisms were associated with a reduced risk of PD (SimónSánchez et al., 2009), prompting further research into ABCA5 function. A recent study has indicated that the levels of the PD pathological hallmark protein α-synuclein are affected by sphingomyelin efflux via the ABCA5 transporter and highlights a new avenue for alleviating the lysosomal burden and α-synuclein levels in PD (Fu et al., 2024).