P2ry1, encoding the purinergic receptor P2Y1, is involved in multiple biological processes. It is part of purinergic signaling pathways where extracellular ATP binds to P2Y1 receptors, triggering various cellular responses. It has significance in the nervous system, pancreas, and diseases such as diabetes and gastric cancer [3,4,5].

In airway protection, optogenetic activation of vagal P2RY1 neurons evokes a coordinated airway defense program including apnea, vocal fold adduction, swallowing, and expiratory reflexes, while ablation of these neurons eliminates protective responses to laryngeal water and acid challenge. In the context of breathing, optogenetic stimulation of P2ry1-expressing vagus nerve afferents acutely silences respiration, trapping animals in exhalation [1,2].

In gastric cancer, high DNA methylation in the P2ry1 promoter region may reduce its mRNA expression, and activation of hypermethylated P2ry1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation [3]. Regarding type 2 diabetes (T2D), sequencing P2yr1 revealed rare variants, some causing impaired glucose control. P2ry1 variants in human islets are linked to T2D risk, and a P2ry1-specific agonist increases insulin secretion upon glucose stimulation [5].

In summary, P2ry1 is crucial for airway protection, breathing regulation, and has implications in gastric cancer and T2D. Mouse models with genetic manipulation of P2ry1, such as ablation in airway-related studies, have provided insights into its functions in these physiological and disease-related processes.