Scarb2, also known as lysosomal integral membrane protein type 2 (LIMP2), is a lysosomal membrane protein. It is involved in various cellular processes, such as cholesterol handling in lysosomes, where it binds cholesterol and may participate in its transport through a transglycocalyx tunnel [3]. It is also linked to several biological pathways and disease conditions. Genetic models, especially KO mouse models, are valuable for studying its functions.

Knockout of Scarb2 in hepatocytes attenuates HCC initiation and progression in MYC-driven and DEN-induced HCC mouse models, indicating that SCARB2 drives hepatocellular carcinoma tumor-initiating cells via enhanced MYC transcriptional activity [1]. In mice, Scarb2 deficiency leads to age-dependent dietary lipid malabsorption, gut dysbiosis, and an altered bile acid pool, impairing epithelium renewal and lipid absorption. Inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice [4]. Also, EV-A71 infection in neonatal mice is mediated by mScarb2, and the severity of the disease, virus spread, and susceptibility period are modulated by mScarb2 expression [2].

In conclusion, Scarb2 is essential in multiple biological processes, including cholesterol handling, lipid absorption, and cancer cell stem-like properties. The use of Scarb2 KO mouse models has revealed its roles in hepatocellular carcinoma, neurodegeneration associated with gut dysfunction, and EV-A71-related diseases, providing insights into disease mechanisms and potential therapeutic targets.