HNMT (histamine N-methyltransferase) is a cytoplasmic enzyme that serves as the primary mechanism for histamine inactivation through N-methylation 1. The enzyme plays a crucial role in histamine catabolism and regulates histamine-mediated physiological responses, particularly in the respiratory system. HNMT is essential for maintaining brain histamine homeostasis, as demonstrated by studies showing that HNMT deficiency results in robust increases in brain histamine concentrations 2. The most clinically relevant polymorphism is rs11558538 (Thr105Ile), which occurs with significant frequency across populations 1. This polymorphism has been associated with reduced risk for Parkinson's disease, with meta-analysis showing protective effects (odds ratio 0.61-0.63) 3. HNMT expression changes have been detected in peripheral blood of early-stage Parkinson's disease patients, suggesting potential involvement in disease pathogenesis 4. The enzyme has also been implicated in cardiovascular disease, with studies identifying HNMT in diabetic vascular metabolic reprogramming 5. Additionally, HNMT shows potential as a biomarker for Parkinson's disease prediction, demonstrating significant association in large-scale proteomic analyses 6. However, functional validation studies suggest HNMT knockout does not significantly affect doxorubicin-induced cardiotoxicity in cardiomyocytes 7.