Purpose of review: Lipase maturation factor 1 (LMF1) is a membrane-bound protein located in the endoplasmic reticulum. It is essential to the folding and assembly (i.e., maturation) of a selected group of lipases that include lipoprotein lipase, hepatic lipase and endothelial lipase. The purpose of this review is to examine recent studies that have begun to elucidate the structure and function of LMF1 and to place it in the context of lipase folding and assembly.
Recent findings: Recent studies identified mutations in LMF1 that cause combined lipase deficiency and hypertriglyceridemia in humans. These mutations result in the truncation of a large, evolutionarily conserved domain (DUF1222), which is essential for interaction with lipases and their attainment of enzymatic activity. The structural complexity of LMF1 has been further characterized by solving its topology in the endoplasmic reticulum membrane. Recent studies indicate that in addition to lipoprotein lipase and hepatic lipase, the maturation of endothelial lipase is also dependent on LMF1. Based on its apparent specificity for dimeric lipases, LMF1 is proposed to play an essential role in the assembly and/or stabilization of head-to-tail lipase homodimers.
Summary: LMF1 functions in the maturation of a selected group of secreted lipases that assemble into homodimers in the endoplasmic reticulum. These dimeric lipases include lipoprotein lipase, hepatic lipase and endothelial lipase, all of which contribute significantly to plasma triglyceride and high-density lipoprotein cholesterol levels in humans. Future studies involving genetically engineered mouse models will be required to fully elucidate the role of LMF1 in normal physiology and diseases.