Probable cation-transporting ATPase 13A2 (ATP13A2)

Probable cation-transporting ATPase 13A2 (ATP13A2) is a lysosomal P5-type ATPase that primarily functions as a polyamine exporter, transporting spermine and spermidine from the lysosomal lumen to the cytosol (UniProt, PubMed: 31996848). It plays a critical role in maintaining lysosomal health, regulating intracellular cation homeostasis (particularly zinc and manganese), and facilitating the clearance of misfolded proteins such as alpha-synuclein (PubMed: 22186024, 24603074). Mutations in the ATP13A2 gene are the primary cause of Kufor-Rakeb syndrome, a rare juvenile-onset form of Parkinsonism, and are also associated with neuronal ceroid lipofuscinosis and hereditary spastic paraplegia (PubMed: 22296644, 28137957). Loss of ATP13A2 function leads to toxic polyamine accumulation, lysosomal dysfunction, and impaired autophagy, which are central to the pathogenesis of several neurodegenerative diseases (Frontiers, PubMed: 30538141). While no drugs currently target ATP13A2 in clinical practice, it is considered a high-priority therapeutic target for Parkinson's disease and other synucleinopathies, with research focusing on small molecule activators to restore its neuroprotective functions (Michael J. Fox Foundation, bioRxiv).

Other names

PARK9Polyamine-transporting ATPase 13A2CLN12HSA9947KRPPDSPG78ATPase 13A2Cation-transporting ATPase 13A2

Therapeutic strategies focus on the activation of ATP13A2 to restore lysosomal polyamine export and enhance the degradation of misfolded proteins like alpha-synuclein. Experimental compounds like DFMO and AMXT 1501 interact with the polyamine pathway to modulate the effects of ATP13A2 deficiency.