Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/ phosphodiesterase 2 (Enpp2), is a secreted lysophospholipase D (lysoPLD) that generates the lipid mediator lysophosphatidic acid (LPA), which in turn activates G protein-coupled receptors to evoke various cellular responses. ATX is essential for normal development, is implicated in various physiological processes, and is also associated with pathological conditions such as cancer, pain and fibrosis. Despite its importance, the molecular mechanism of ATX-catalyzed LPA production has long been elusive. Recent structural analyses have provided new insights into the mechanisms of localized and regulated LPA production by ATX. This structural information will pave the way for further biochemical, biological and medical research.
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