Moreover, the insertion of two leucines in the signal peptide has been reported in a family with familial combined hyperlipidemia and two patients with FH (Abifadel et al., 2008) and in vitro studies have shown that it causes a reduction in the secretion of the mature form of PCSK9 compared to the wild type PCSK9 (Benito-Vicente et al., 2022). This evidence concerns the gene PCSK9 and hyperlipidemia.