Give me A5 for lipoprotein hydrolysis!

AIPOA5 is a newly identified apolipoprotein that plays a crucial role in the regulation of plasma triglyceride levels. In several human studies, common APOA5 single nucleotide polymorphisms have been strongly associated with elevated plasma triglyceride levels. In this issue of the JCI, Marcais et al. report that the rare Q139X mutation in APOA5 leads to severe hypertri-glyceridemia by exerting a dominant-negative effect on die plasma lipolytic system for triglyceride rich, lipoproteins (see the related article beginning on page 2862). The presented data support the idea that the molecular mechanism of APOA5 function may include the enhancement of binding between lipoproteins and proteoglycans at the vascular wall and activation of proteo-glycan-bound lipoprotein lipase.