ATPase phospholipid transporting 8A2 (ATP8A2)

ATPase phospholipid transporting 8A2 (ATP8A2) is a member of the P4-ATPase family (class I type 8A) that catalyzes ATP-dependent “flipping” of aminophospholipids, especially phosphatidylserine and, to a lesser extent, phosphatidylethanolamine, from the exoplasmic to the cytosolic leaflet of the lipid bilayer. This activity is critical for maintaining asymmetric membrane phospholipid distribution, essential for cell function, especially in the nervous system. ATP8A2 is highly expressed in the brain, retina, testis, and spinal cord, where it supports photoreceptor cell membrane maintenance, neuronal survival, and vesicle trafficking. Mutations in ATP8A2 cause severe neurodevelopmental disorders, including cerebellar ataxia with mental retardation and disequilibrium syndrome (CAMRQ4), and are associated with symptoms such as hypotonia, chorioretinal degeneration, movement disorders, and cognitive impairment[1][2][3][6]. ATP8A2 functions in complex with its accessory β-subunit TMEM30A (CDC50A) and is essential for normal visual and auditory system development[2][3]. No approved drugs currently target ATP8A2 directly, and loss of its function poses challenges for therapeutic modulation because of the risk of neurotoxicity.

Other names

Phospholipid-transporting ATPase IBATPIBML-1ATPase, aminophospholipid transporter, class I, type 8A, member 2ATPase, aminophospholipid transporter-like, class I, type 8A, member 2P4-ATPase flippase complex alpha subunit ATP8A2CAMRQ4

Drugs targeting this molecule would modulate phospholipid asymmetric distribution by altering flippase activity; no drugs have been clearly identified targeting ATP8A2 as of now[1][2].