ATPase cation-transporting 13A2 (ATP13A2)

ATP13A2 (ATPase cation-transporting 13A2, also known as PARK9) is a **P-type ATPase transporter** predominantly localized to the lysosomal membrane, where it plays a critical role in **polyamine transport and maintaining lysosomal function**[1][2][3]. Structurally, it contains ten transmembrane domains and three main cytosolic domains involved in ATP binding, phosphorylation, and substrate translocation. It specifically transports polyamines such as spermine from the lysosomal lumen to the cytosol, tightly regulating polyamine homeostasis. Disruption of ATP13A2—via genetic mutations—leads to impaired polyamine export, lysosomal dysfunction, and subsequently contributes to the pathogenesis of several neurodegenerative diseases, including Kufor-Rakeb syndrome (an early-onset, autosomal recessive form of Parkinsonism), hereditary spastic paraplegia, and neuronal ceroid lipofuscinosis[1][2][3]. Besides its key role in neuroprotection, ATP13A2 is involved in lysosome-autophagosome fusion and regulates responses to cellular stress, highlighting its therapeutic relevance for neurodegenerative disorders. To date, it is primarily a genetic and mechanistic target for research rather than a therapeutic target for approved drugs.

Other names

PARK9Polyamine-transporting ATPase 13A2HSA9947CLN12KRPPDSPG78probable cation-transporting ATPase 13A2

For experimental inhibitors/activators: Modulation of ATPase/phosphorylation cycle impacts polyamine transport and lysosomal function