Familial hypertriglyceridemia has been suggested to be an autosomal dominant condition with age-dependent penetrance, but so far the underlying defective gene has not been elucidated. LPL gene and apolipoprotein A-I/C-III/A-IV gene cluster might be involved in familial clustering of hypertriglyceridemia. Heterozygous LPL deficiencies caused by several types of gene mutation are known to result in a partial defect in catabolism of VLDL, occurring mild to moderate hypertriglyceridemia. However, although the mutation of LPL gene results in reduced lipolytic activity, this type of dyslipidemia appears to manifest only if VLDL-TG production is also increased. These suggest that overproduction of VLDL-TG is a more important cause of hypertriglyceridemia than is the LPL deficiency. Moreover, families with a clustering of hypertriglyceridemia are known to be at increased risk of hyperinsulinemia due to impaired insulin sensitivity. Impaired insulin sensitivity and hyperinsulinemia are the major determinants of excessive VLDL-TG synthesis and dyslipidemia. Taken together, abnormally high production of VLDL-TG seemed to be the major factor in causing familial hypertriglyceridemia, but clearance capacity can play an important role in determining the severity of the TG elevation.