Phospholipid-transporting ATPase 10B (ATP10B) (ATP10B)

Phospholipid-transporting ATPase 10B (ATP10B) is a member of the P4-type ATPase family, functioning as a lipid flippase that translocates phospholipids across biological membranes (UniProt O94823). Specifically, ATP10B is localized to late endosomes and lysosomes, where it transports glucosylceramide (GlcCer) and phosphatidylcholine (PC) from the exoplasmic/luminal leaflet to the cytosolic leaflet (Martin et al., 2020, Genetics in Medicine). This activity is crucial for maintaining the lipid composition of the lysosomal membrane and ensuring proper lysosomal function and endo-lysosomal trafficking. Genetic studies have identified ATP10B as a risk factor for Parkinson's disease and dementia with Lewy bodies, as loss-of-function mutations lead to the accumulation of GlcCer and PC within lysosomes (Smolders et al., 2020, Molecular Psychiatry). This accumulation results in lysosomal dysfunction, impaired clearance of protein aggregates like alpha-synuclein, and increased neuronal vulnerability to cellular stress. While there are currently no approved drugs targeting ATP10B, it represents a promising therapeutic target for neurodegenerative disorders, where pharmacological activation or stabilization of the transporter could potentially restore lysosomal health and mitigate disease progression (Vangheluwe et al., 2020, Biochemical Society Transactions).

Other names

ATP10BProbable phospholipid-transporting ATPase VBP4-ATPase flippase ATP10BATPase phospholipid transporting 10B

Currently, no drugs are approved that target ATP10B. Potential therapeutic strategies involve the development of small molecule activators or gene therapies designed to restore or enhance its flippase activity, thereby facilitating the transport of glucosylceramide and phosphatidylcholine out of the lysosomal lumen to prevent lipid accumulation and lysosomal stress.