The article reviews the role of phenylacetylglutamine (PAGln), a gut bacteria-derived metabolite, in various diseases. PAGln is produced from the microbial metabolism of phenylalanine, a dietary amino acid, and is conjugated with glutamine and glycine in the liver and kidneys. The review highlights the biochemical and microbial synthesis of PAGln, its excretion through the kidneys, and its association with cardiovascular, cerebrovascular, and neurological diseases. PAGln is linked to thrombosis and platelet activation, which can exacerbate cardiovascular and cerebrovascular conditions. It also plays a role in the progression of neurological disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. The review discusses the potential of PAGln as a biomarker and therapeutic target for these diseases, emphasizing the need for further research to understand its mechanisms and clinical implications.The article reviews the role of phenylacetylglutamine (PAGln), a gut bacteria-derived metabolite, in various diseases. PAGln is produced from the microbial metabolism of phenylalanine, a dietary amino acid, and is conjugated with glutamine and glycine in the liver and kidneys. The review highlights the biochemical and microbial synthesis of PAGln, its excretion through the kidneys, and its association with cardiovascular, cerebrovascular, and neurological diseases. PAGln is linked to thrombosis and platelet activation, which can exacerbate cardiovascular and cerebrovascular conditions. It also plays a role in the progression of neurological disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. The review discusses the potential of PAGln as a biomarker and therapeutic target for these diseases, emphasizing the need for further research to understand its mechanisms and clinical implications.