Atp11b, a member of the P4-ATPase family, preferentially translocates phosphatidylserine of the cell membrane. It is involved in multiple biological processes and associated with various pathways, playing a significant role in normal physiological functions and disease conditions. Genetic models, such as gene knockout (KO) mouse models, are valuable tools for studying its functions [5].

In KO mouse models, Atp11b deficiency leads to abnormal neural and dendritic morphology in the hippocampus, impairs synaptic plasticity through the MAPK14 signaling pathway [1]. It also causes excessive fatty acid uptake, abnormal neutral lipid synthesis and mitochondrial energy metabolism in microglia, resulting in the accumulation of pathological lipid droplets in microglia and AD mice, while its overexpression alleviates AD-related impairments [2]. In addition, Atp11b deletion affects the gut microbiota in mice, increasing pro-inflammatory bacteria and decreasing probiotics, which accelerates brain aging [4]. In cancer research, low expression of ATP11B in breast cancer is associated with enhanced metastasis due to increased non-apoptotic phosphatidylserine on the cell membrane, and targeting the ATP11B-related axis may prevent metastasis [3]. Also, in pancreatic cancer, ATP11B is a critical regulator in maintaining PD-L1 expression, and its depletion promotes PD-L1 degradation, reactivating the immune microenvironment [6].

In conclusion, Atp11b plays essential roles in synaptic plasticity, microglial lipid metabolism, brain aging, and cancer metastasis. The study of Atp11b using KO mouse models provides insights into the pathogenesis of neurodegenerative diseases like Alzheimer's disease and cancer metastasis, offering potential therapeutic targets for these diseases.