Abstract: Lysophosphatidic acid (LPA) is a pleiotropic lipid agonist essential for functions of the central nervous system (CNS). It is abundant in the developing and adult brain while its concentration in biological fluids, including cerebrospinal fluid, varies significantly (Figure 1Α; Yung et al., 2014). LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities (Figure 1Α; Yung et al., 2014; Hernández-Araiza et al., 2018). During CNS development, LPA influences critical processes such as cell proliferation, survival, and differentiation, promotes neuronal migration, and affects neuronal morphology (Yung et al., 2014). Furthermore, LPA mediates cortical development, myelination, pain, synaptic transmission, and plasticity (Yung et al., 2014). Deregulation of LPA signaling contributes to a myriad of CNS pathologies including psychiatric diseases, neurodegeneration, neuropathic pain, neuroinflammatory, and traumatic conditions (Yung et al., 2014).