Lysophosphatidic acid receptor 5 (LPAR5) (LPAR5)

Lysophosphatidic acid receptor 5 (LPAR5), also known as GPR92, is a G protein-coupled receptor that functions as a critical inhibitory checkpoint on CD8+ T cells [Matas-Rico et al., 2016, J Exp Med]. In the tumor microenvironment, elevated levels of lysophosphatidic acid (LPA) bind to LPAR5, triggering a signaling cascade that suppresses T-cell receptor (TCR) activation [Oda et al., 2017, Sci Rep]. This signaling inhibits the production of cytotoxic molecules like granzyme B and interferon-gamma, effectively dampening the immune system's ability to destroy malignant cells [Krieger et al., 2020, Nat Commun]. Consequently, LPAR5 has emerged as a promising target for cancer immunotherapy, with small-molecule antagonists being developed to restore T-cell effector functions [Oda et al., 2017, Sci Rep]. Beyond its role in oncology, LPAR5 is involved in platelet activation and the modulation of inflammatory pain [UniProt, 2024, Q9H1C0]. These non-immune functions present both alternative therapeutic opportunities and potential safety considerations for drug development [UniProt, 2024, Q9H1C0]. Current research focuses on using LPAR5 inhibitors to enhance the efficacy of existing checkpoint inhibitors like PD-1/PD-L1 blockers [Krieger et al., 2020, Nat Commun].

Other names

LPA5GPR92G-protein coupled receptor 92Lysophosphatidic acid receptor 5

Antagonism of LPAR5 to prevent LPA-mediated inhibition of T-cell receptor (TCR) signaling and restore CD8+ T cell effector function [Oda et al., 2017, Sci Rep].