Atp8a1, a member of the P4-ATPase family, is a phospholipid flippase. It is involved in the translocation of phosphatidylserine and phosphatidylethanolamine across lipid bilayers, maintaining lipid asymmetry in eukaryotic cells. This function is crucial for various cellular processes, including membrane trafficking, cell-cell communication, and apoptosis regulation [1,2,4,5,6,7].

Global Atp8a1 knockout mice studies showed that it is dispensable for spermatogenesis and male fertility as mutant mice were fertile with comparable sperm count and motility to controls [1]. In contrast, Atp8a1 deletion in mice increased the proliferative activity of hematopoietic stem cells by impairing PTEN function, leading to slight hyperleukocytosis [2]. Also, loss of ATP8A1 in mouse hippocampal neurons recapitulated the defect in synaptic vesicle mobilization at high frequency observed with loss of adaptor protein AP-3 [3].

In conclusion, Atp8a1 plays a significant role in maintaining lipid asymmetry, which impacts multiple biological processes. Gene knockout mouse models have been instrumental in revealing its functions in spermatogenesis, hematopoiesis, and synaptic vesicle release. These findings contribute to our understanding of related physiological and pathological mechanisms [1,2,3].