PTGS2 (prostaglandin-endoperoxide synthase 2), also known as COX-2, is a dual cyclooxygenase/peroxidase enzyme that catalyzes the rate-limiting step in prostaglandin biosynthesis from arachidonic acid and other polyunsaturated fatty acids 1. The enzyme sequentially oxygenates arachidonic acid to prostaglandin G2 (PGG2) and reduces it to prostaglandin H2 (PGH2), the precursor for all 2-series prostaglandins and thromboxanes 2. PTGS2 also generates specialized pro-resolving mediators and lipid mediators involved in inflammatory resolution and pain responses. Elevated PTGS2 expression occurs early in colorectal cancer development, appearing in adenomatous tissue and correlating with increased cancer risk through specific gene polymorphisms 1. In colorectal cancer progression, TFF3 binding to CD147 activates STAT3-mediated PTGS2 expression, producing PGE2 that promotes tumor cell migration and invasion via EP4 receptor signaling 3. PTGS2 plays critical roles in reproductive processes, including fertilization and early embryo development through oviductal prostaglandin signaling 2. In melanoma, STAT1-mediated PTGS2 upregulation promotes ferroptosis, suggesting therapeutic potential 4. PTGS2 also participates in ferroptosis and pyroptosis pathways in coronary atherosclerosis, where it functions as a hub gene linked to disease severity 5. These findings establish PTGS2 as a critical mediator in inflammation, cancer progression, reproductive biology, and ferroptotic cell death pathways.