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Lysophosphatidic acid (LPA), a bioactive phospholipid, and its family of cognate G protein-coupled receptors have demonstrated roles in many biological functions in the nervous system. To date, five LPA receptors have been identified, and additional receptors may exist. Most of these receptors have been genetically deleted in mice toward identifying biological and medically relevant roles. In addition, small molecule agonists and antagonists have been reported. Here we review recent data on the nervous system functions of LPA signaling, and summarize data on reported agonists and antagonists of LPA receptors.