A spectrum of disorders, ranging from rare severe cases of homozygous null 
lipoprotein lipase deficiency (LPLD)-familial chylomicronemia syndrome (FCS) to 
heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia 
and pancreatitis. The effects of mutations are exacerbated by environmental 
factors such as diet, pregnancy, and insulin resistance. Areas covered: In this 
review, authors discuss chronic treatment of FCS by ultra-low fat diets allied 
with the use of fibrates, omega-3 fatty acids, niacin, statins, and 
insulin-sensitizing therapies depending on the extent of residual lipoprotein 
lipase (LPL) activity; novel therapies in development target triglyceride 
(TG)-rich lipoprotein particle clearance. Previously, a gene therapy approach to 
LPL-alipogene tiparvovec showed that direct targeting of LPL function reduced 
pancreatitis events. An antisense oligonucleotide to apolipoprotein-C3, 
volanesorsen has been shown to decrease TGs by 70-80% and possibly to reduce 
rates of pancreatitis admissions. Studies are underway to validate its long-term 
efficacy and safety. Other approaches investigating the role of LPL modulating 
proteins such as angiopoietin-like petide-3 (ANGPTL3) are under consideration. 
Expert opinion: Current therapeutic options are not sufficient for management of 
many cases of FCS. The availability of antisense anti-apoC3 therapies and, in 
the future, ANGPTL3 therapies may remedy this.