FMO3 is a hepatic flavin-dependent monooxygenase that catalyzes the oxidation of nitrogen- and sulfur-containing compounds, including drugs and dietary constituents 123. Its primary physiological role involves metabolizing trimethylamine (TMA)—produced by gut microbiota from dietary precursors like choline, betaine, and L-carnitine—into the non-volatile trimethylamine N-oxide (TMAO) 4. This metabolism is functionally important: by regulating TMAO concentration, FMO3 modulates platelet responsiveness and thrombus formation 5. Beyond TMA metabolism, FMO3-generated TMAO has broader metabolic consequences. TMAO binds and activates PERK, a kinase controlling endoplasmic reticulum stress responses, thereby inducing FoxO1 and promoting metabolic dysfunction 6. Elevated TMAO levels are implicated in cardiovascular, renal, and neurodegenerative diseases 6. Common FMO3 genetic variants moderately reduce enzyme activity and can alter drug metabolism efficacy or toxicity 7. Clinically, severe FMO3 deficiency causes trimethylaminuria (fish-odor syndrome), characterized by accumulation of odorous TMA in breath, sweat, and urine, causing significant psychosocial burden 89. Recent evidence demonstrates FMO3's role in decidualization and reproductive health, with endometrial TMAO synthesis being critical for preventing recurrent spontaneous abortion 10.