Ldlr, short for low-density lipoprotein receptor, is a crucial protein that plays a key role in cholesterol metabolism. It binds to low-density lipoproteins (LDL), facilitating their internalization into cells, thus regulating plasma LDL-cholesterol levels. This process is integral to the normal lipid metabolism pathway and is of great biological importance in maintaining cardiovascular health [2,3,6]. Genetic models, such as gene knockout mouse models, have been instrumental in studying Ldlr function.

In gene knockout studies, Ldlr-deficient (Ldlr-/ -) mice have been used to model familial hypercholesterolemia (FH). These mice exhibit elevated LDL cholesterol levels, leading to increased lipid deposition in the liver, more atherosclerotic plaques, and inflammation [3]. In the context of Crimean-Congo hemorrhagic fever virus (CCHFV) infection, genetic knockout of Ldlr in various CCHFV-susceptible human, monkey, and mouse cells impairs viral infection. This indicates that Ldlr is an entry receptor for CCHFV, and blocking Ldlr can reduce viral loads, pathological effects, and death in infected mice [1,4]. Also, in pulmonary fibrosis, Ldlr-/-mice treated with bleomycin show higher LDL levels, more apoptosis, increased fibroblast-like cells, and more severe fibrotic responses compared to wild-type mice, suggesting that Ldlr dysfunction promotes pulmonary fibrosis [5].

In conclusion, Ldlr is essential for cholesterol metabolism and plays significant roles in diseases like FH, CCHFV infection, and pulmonary fibrosis. Gene knockout mouse models have been pivotal in uncovering these functions, providing valuable insights into the underlying mechanisms and potential therapeutic targets for these disease areas.