Klb, also known as β -Klotho, is a co-receptor for fibroblast growth factor 15/19 (FGF15/19) and FGF21 [2]. It is a vital element of the FGF receptor complex, facilitating the binding of FGF19 and FGF21 to the FGFRs on target cells, thus playing a crucial role in FGF-mediated signaling pathways which are involved in multiple biological processes such as metabolism, muscle development, and liver function [4].

In intrauterine growth restriction (IUGR), increased KLB levels in fetal muscle were associated with reduced myogenic capacity, and transfection of muscle progenitor cells with KLB small interfering RNA promoted myogenesis, suggesting KLB mediates impaired muscle development in IUGR [1]. In hepatic lipid metabolism, high-fat diet (HFD)-induced methylation at the Klb promoter down-regulated Klb expression, leading to hepatic steatosis, while liver-specific deletion of Dnmt1 or 3a increased Klb expression and ameliorated HFD-induced hepatic steatosis [2]. Also, in the context of ketogenic diet (KD), impairing liver FGF21-KLB signaling via KLB knockdown diminished the beneficial effects of KD on hepatic steatosis, insulin resistance, and lipid metabolism regulation [3].

In conclusion, Klb is essential in multiple biological processes. Its role in muscle development in IUGR, hepatic lipid metabolism, and the beneficial effects of KD on metabolic disorders has been revealed through various genetic manipulation models. Understanding Klb function provides insights into the pathogenesis of IUGR, fatty liver diseases, and metabolic disorders, potentially guiding the development of new therapeutic strategies for these conditions.