P2ry2, a G protein-coupled receptor of the purinergic receptor family, is involved in multiple biological processes. It participates in regulating cell proliferation, apoptosis, and is associated with pathways such as PI3K-AKT, which is crucial for cell survival and growth. It also plays a role in purinergic signaling, which has implications for nerve development, peripheral neuropathies, and cell-to-cell communication [1,6].

In acute myeloid leukemia (AML), selinexor, an XPO1 inhibitor, activates PI3Kγ-dependent AKT signaling in AML cells by upregulating P2ry2. Inhibiting this P2ry2-AKT axis potentiates the anti-leukemic effects of selinexor in AML cell lines, patient-derived primary cultures, and mouse models of AML [1].

In cerebral ischemia-reperfusion injury, up-regulated P2ry2 can alleviate the injury by inhibiting YAP phosphorylation and reducing mitochondrial fission, as seen in rat middle cerebral artery occlusion and PC12 cell oxygen-glucose deprivation/reoxygenation models [2].

In gastric cancer, P2ry2 activates the AKT/GSK-3beta/VEGF signal to promote the proliferation and migration of gastric cancer cells [3].

In an allergic airway inflammation mouse model, P2ry2-deficient mice in alveolar epithelial cells, hematopoietic cells, myeloid cells, or dendritic cells showed reduced signs of acute airway inflammation [4].

In a lipopolysaccharide-induced acute respiratory distress syndrome (ARDS) mouse model, blocking P2ry2 attenuated inflammation, and P2ry2 expression in neutrophils was associated with ARDS-caused inflammatory features [5].

In conclusion, P2ry2 plays diverse and significant roles in multiple biological processes and disease conditions. The use of gene knockout and conditional knockout mouse models in these studies has been crucial in revealing its functions in diseases such as AML, cerebral ischemia-reperfusion injury, gastric cancer, allergic airway inflammation, and ARDS, providing potential therapeutic targets for these diseases.