Phospholipids, the major components of biological membranes, usually have two fatty acids. Less common are the lysophospholipids, which have only one fatty acid. Like prostaglandins and leukotrienes, some lysophospholipids serve as mediators to regulate various cellular functions through G protein-coupled receptors (GPCRs). This review focuses on a lysophospholipid with an inositol head, lysophosphatidylinositol (LPI), and summarizes its distribution, alterations, metabolic mechanisms, and physiological and pathological functions. In addition, we will summarize the current knowledge of GPR55, a proposed G protein-coupled receptor for LPI, with a particular focus on its functions in cancer and immune responses.