LAUSR

For more than half a century, a mystery shrouded the enzyme that breaks down triglycerides in the bloodstream: How does the enzyme, lipoprotein lipase, get from the interstitial spaces to its site of action inside blood vessels? This mystery intrigued Stephen G. Young, a cardiologist at the University of California, Los Angeles. Through more than 15 years of research, Young and his University of California, Los Angeles faculty collaborators, Loren Fong and Anne Beigneux, uncovered a protein called GPIHBP1 that not only captures and moves lipoprotein lipase into blood vessels but stabilizes the enzyme as well. Understanding how GPIHBP1 works allowed Young and colleagues to solve the structure of lipoprotein lipase and to identify a treatment for a subset of patients with severe hypertriglyceridemia (chylomicronemia), a disorder in which the body’s ability to break down fats is impaired, often leading to acute pancreatitis. In his Inaugural Article (1), Young reviews the long arc of his research on this important protein and its role in the metabolism of plasma triglycerides. PNAS recently spoke with Young about this work.