Nevertheless, further studies are required to determine whether hyperlipidemia alone is sufficient to drive ISC hyperproliferation in vivo using other hyperlipidemic models to circumvent the potential impact of Ldlr deficiency in the intestine, such as Ldlr liver-specific knockout mice or hepatic overexpression of PSCK9, which is known to cause hyperlipidemia by facilitating the degradation of LDLR in the liver. Here, LDLR is linked to hyperlipidemia.