Phosphatidylcholine-specific phospholipase D (PC-PLD) is an enzyme that plays a pivotal role in the regulation of cellular processes through its involvement in the hydrolysis of phosphatidylcholine to generate phosphatidic acid and choline. Phosphatidic acid acts as a second messenger in various signaling pathways, thereby influencing a host of cellular functions, including but not limited to membrane trafficking, secretion, cell survival, and proliferation. The expression of PC-PLD is tightly controlled within cells, and dysregulation of this enzyme can lead to alterations in cellular homeostasis. Given its central role in critical cellular mechanisms, the modulation of PC-PLD expression is an area of significant interest, particularly in the context of understanding the molecular basis of its regulation.Research has identified a number of chemical compounds that can potentially influence the expression of PC-PLD. One such compound is Triptolide, a diterpene triepoxide found in the plant Tripterygium wilfordii, which has been shown to downregulate the expression of certain genes at the transcriptional level. Another noteworthy compound is Curcumin, a polyphenol from the spice turmeric, which can decrease the expression of enzymes by inhibiting key signaling pathways such as NF-κB. Compounds like Epigallocatechin gallate (EGCG), found in green tea, can alter gene expression by modifying the epigenetic landscape, leading to changes in chromatin structure and transcription factor accessibility to DNA. Similarly, Resveratrol, a compound found in red wine, grapes, and berries, has been known to downregulate enzyme expression by influencing sirtuin activity, which can alter the acetylation state of histones associated with gene promoters. In the quest to understand the regulation of PC-PLD expression, these compounds, among others, serve as valuable tools in dissecting the complex network of cellular signaling and gene expression control. Their diverse mechanisms of action reflect the intricate nature of cellular regulation and underscore the potential for chemical biology to unlock the secrets of enzyme regulation within the cellular milieu.