ENPP2 and rheumatoid arthritis: One recent study suggested that LPA stimulation can induce the development of macrophages through induction of Akt/mTOR signaling pathway and PPARγ activation in mice and humans, indicating that LPA is capable of regulating immune defense mechanisms (49) Accordingly, it is possible that reduced LPA levels in the Atx-deficient mice may dampen the macrophage development and relevant inflammatory responses like rheumatoid arthritis, leading to compromised immunity.