LPAR5 (lysophosphatidic acid receptor 5) is a G protein-coupled receptor that mediates diverse cellular responses to lysophosphatidic acid (LPA) signaling 1. The receptor plays crucial roles in skin barrier function, where it promotes keratinocyte differentiation and filaggrin expression through the LPAR1/LPAR5-RHO-ROCK-SRF pathway, contributing to skin homeostasis and protection against allergens and pathogens 2. In nociception, LPAR5 is expressed in dorsal root ganglion neurons and skin keratinocytes, where it mediates itch responses, particularly non-histaminergic itch induced by compounds like hydroxychloroquine 3. LPAR5 has significant implications in cancer biology, where it promotes epithelial-to-mesenchymal transition (EMT) and radioresistance through ERK/Snail pathway activation 4. The receptor's expression is regulated by epigenetic mechanisms, including PARP1-mediated chr12 accessibility control of METTL3, which affects LPAR5 mRNA m6A methylation and stability 5. In the tumor microenvironment, LPAR5 expression in macrophages correlates with better prognosis in osteosarcoma and serves as a potential therapeutic target 6. Additionally, LPAR5 modulates neuroinflammation, as its suppression by PARP14 inhibits microglial activation and promotes post-stroke recovery 7.