GPR92 (now named as lysophosphatidic acid receptor 5, LPAR5) is a 7-transmembrane receptor that senses a bioactive lipid, lysophosphatidic acid. Gene deficiency of Lpar5 showed protection against the development of neuropathic pain. Because expression of LPAR5 has been found in mast cells, macrophages, and microglia, in this study, we investigated the therapeutic potential of LPAR5 in allergic asthma. We used a selective LPAR5 antagonist (6,7-dimethoxy-2-(5-methyl-1,2-benzisoxazol-3-yl)-4-(1-piperidinylcarbonyl)-1(2H)-isoquinolinone (HY-114379) in both an in vitro mast cell degranulation assay and an in vivo ovalbumin-induced asthma model in BALB/c mice. In RBL-2H3 cells expressing the lpar5 gene, HY-114379 treatment attenuated antigen-induced degranulation. In vivo, administration of HY-114379 reduced airway resistance triggered by ovalbumin exposure. Histopathological analysis additionally demonstrated diminished pulmonary inflammation following HY-114379 administration, accompanied by significant reductions in cytokine expression within lung tissue. Furthermore, treatment with HY-114379 led to a decrease in eosinophil and lymphocyte infiltration, as well as reduced levels of inflammatory cytokines in bronchoalveolar lavage fluid. In summary, these findings suggest that pharmacological inhibition of LPAR5 using HY-114379 attenuates key features of allergic asthma, supporting LPAR5 as a potential therapeutic target for the disease condition.