Human induced pluripotent stem cells (hiPSC) are becoming a relevant model for the study of liver metabolic diseases once differentiated into hepatocyte-like cells (HLC), and it has been shown that they can faithfully recapitulate autosomal dominant hypercholesterolemia (ADH). PCSK9 is a critical modulator of cholesterol homeostasis, and quickly became a hot target for ADH pharmacological treatment strategies. However, current cellular models to further decipher the role of PCSK9 in ADH are limited, especially to study the PCSK9 gain of function mutation S127R, which seems to interfere with LDL cholesterol homeostasis intracellularly by still unknown mechanisms.

(From CHOPIN project)