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The klotho family protein klotho beta （KLB） is a single transmembrane protein that serves as a co-receptor with fibroblast growth factor receptor （FGFR）. By mediating FGF21 binding to FGFR, klotho beta plays key roles in the regulation of metabolism. In mice, moreover, decreased klotho beta expression appears to result in FGF21 resistance. This suggests FGF21-KLB-FGFR signaling may be involved in the pathogenesis of NAFLD. An association between klotho beta reduction and fibrosis has been recently reported by Somm et al. who demonstrated that KLB deficient mice exhibited a pro-inflammatory status and onset of fibrosis. Klotho beta functions as a key cell-surface regulator of GSIS by coupling the GP130 receptor signaling to glucose catabolism in β-cells and represents a promising therapeutic target for diabetes.