S1PR2 Signaling in the Lung: Understanding Its Role in Health and Disease.

Sphingosine-1-phosphate receptors (S1PRs) are a family of G protein-coupled transmembrane proteins that play essential roles across nearly all organ systems, including the regulation of pulmonary physiology and immune responses. Expressed across diverse lung cell types, S1PRs mediate critical biological processes such as vascular barrier integrity, immune cell trafficking, and inflammation. While the signaling pathways and physiological functions of S1PR1 and S1PR3 have been extensively characterized, the role of S1PR2 remains less clearly defined and context-dependent. In this review, we summarize current knowledge on S1PR2 signaling within major pulmonary cell populations and explore its contribution to lung homeostasis and disease. By synthesizing evidence from molecular, cellular and in vivo studies, this review aims to summarize the current understanding of S1PR2 signaling across major pulmonary cell populations and its roles in lung homeostasis and disease. The findings of this study could help develop new strategies for treating pulmonary disorders and other diseases by targeting S1PR2.