Atp11a, encoding a P-type ATPase, functions as a flippase at the plasma membrane, translocating phospholipids such as phosphatidylserine from the exoplasmic to the cytoplasmic leaflet, which is crucial for maintaining cellular function and vitality [1,2,3,4]. It is involved in various biological processes and is associated with multiple pathways, though the exact pathways are still being elucidated. Genetic models, especially mouse models, are valuable for studying its functions.

In mouse models, Atp11a -deficient embryos die around E14.5 with thin-walled heart ventricles, and the Atp11a-null mutation in the placenta causes poor development of the labyrinthine layer with unfused trophoblasts, indicating its importance in placental and embryonic development [2]. Conditional Atp11a knockout mice show a progressive reduction of the spiral ganglion neuron compound action potential, recapitulating the human phenotype of autosomal-dominant auditory neuropathy type 2 [1]. A mouse carrying a sublethal ATP11A mutation with neurological deterioration shows aberrant phosphatidylcholine flipping in plasma membranes [4].

In conclusion, Atp11a is essential for maintaining normal cellular phospholipid distribution and is crucial for processes like placental development, auditory nerve function, and neural development. Gene knockout and conditional knockout mouse models have significantly contributed to understanding its role in diseases such as auditory neuropathy, developmental heart disease, and neurological disorders.