PLD1 (phospholipase D1) functions as a phospholipase that selectively hydrolyzes phosphatidylcholine to produce phosphatidic acid and choline 1. The enzyme contains two highly conserved HKD motifs essential for catalysis and dimerization, and is regulated by protein kinase C and small GTPases of the Rho and ARF families 1. PLD1 plays critical roles in multiple cellular processes including signal transduction, membrane trafficking, and mitosis regulation. In oocyte meiosis, PLD1 promotes spindle assembly and migration by maintaining levels of ACTR2, PtdIns(4,5)P2, and phosphorylated cofilin through modulation of autophagy flux 2. The enzyme negatively regulates autophagosome formation, with its depletion leading to increased autophagosome formation and upregulated phosphatidic acid content 3. In cancer contexts, PLD1 contributes to chemoresistance through non-enzymatic interactions with NPM1, promoting nuclear translocation and transcriptional upregulation of IL7R, which activates JAK1/STAT5/BCL-2 signaling pathways 4. PLD1 has also been implicated in cancer stemness and drug resistance through cross-talk between PI3K/Akt and Wnt/β-catenin pathways 5. Additionally, exome sequencing studies have identified PLD1 associations with brain imaging phenotypes and neural development 6.