It turned out that indeed the gene coding for PCSK9 is the one responsible for observed hypercholesterolemia phenotype observed in two French families, with the rare gain-of-function (GOF) mutations S127R and F216L of human PCSK9.4 For a more extensive review of the huge amount of detective work that led to this conclusion, the reader is referred to an excellent review of the history of the identification of PCSK9 as the third FH locus from their genetic perspective.39 The gene discussed is PCSK9; the disease is Hypercholesterolemia.