ATP9A is a Class II P4-ATPase lipid flippase primarily localized to endosomal compartments and the trans-Golgi network 1, functioning as a CDC50-independent monomer with unique gating mechanisms 2. Its primary role involves regulating endosomal cargo recycling through modulation of RAB5 and RAB11 small GTPase activities 1, directing recycling endosome-to-plasma membrane trafficking and retrograde endosome-to-trans-Golgi transport. ATP9A works with MON2 and DOP1B to regulate SNX3 retromer-mediated sorting, preventing Wnt transporter WLS from lysosomal degradation 3. The protein also participates in exocytic Golgi-to-plasma membrane transport via phospholipid substrate recognition, preferentially binding negatively charged phospholipids including phosphatidylserine and phosphoinositides 2. ATP9A negatively regulates extracellular vesicle/exosome release and modulates exosomal lipid composition 4. Biallelic loss-of-function variants cause autosomal recessive neurodevelopmental disorders characterized by intellectual disability, ADHD, hypotonia, and impaired synaptic transmission 1, while de novo heterozygous missense variants also cause intellectual disability with dendritic spine defects 5. ATP9A deficiency in mice recapitulates human neurological phenotypes, including memory deficits and hyperkinetic movement 1. Additionally, ATP9A controls phosphoinositide membrane asymmetry, and its deficiency causes neomycin sensitivity 6.