ATP10B is a late endosomal/lysosomal P4-ATPase that functions as a lipid flippase catalyzing ATP-dependent translocation of glucosylceramide (GluCer) and phosphatidylcholine (PC) from the outer to inner leaflet of lysosomal membranes 1. The protein requires its obligatory subunit CDC50A for activity and contains dileucine residues in its N-terminal region critical for endosomal targeting 2. Beyond canonical lysosomal lipid export, ATP10B facilitates cellular PC uptake under mitochondrial stress conditions 3. Dysfunction of ATP10B compromises lysosomal integrity and general lysosomal function, leading to impaired cellular protection against environmental toxins such as rotenone and manganese 1. Loss of ATP10B in dopaminergic neurons causes progressive degeneration of the nigrostriatal system, manifesting as parkinsonian motor deficits and loss of dopaminergic terminals 4. Compound heterozygous ATP10B mutations have been identified in early-onset Parkinson's disease and dementia with Lewy bodies patients 15. However, the pathogenic significance remains controversial; some genetic association studies in large cohorts failed to establish a clear link between rare ATP10B variants and PD risk 67, indicating that while mechanistically ATP10B loss impairs neuronal survival, its role as a primary PD genetic factor requires further validation.