KLB (klotho beta) functions as a co-receptor for fibroblast growth factor signaling, particularly enabling FGF21 binding to FGFR1 and FGFR4 1. The FGF21-FGFR1-KLB signaling pathway plays critical roles in metabolic homeostasis, promoting lipid catabolism and energy expenditure in white and brown adipose tissues 1. Beyond metabolism, KLB-mediated FGF21 signaling demonstrates protective effects in multiple organ systems. In the kidney, KLB activation by GLP-1 receptor agonists suppresses ferroptosis through AMPK pathway activation, thereby alleviating diabetic kidney injury by regulating iron metabolism and antioxidant responses 2. Similarly, in pulmonary fibrosis, the FGF21-FGFR1-KLB pathway exerts antifibrotic effects by inhibiting alveolar epithelial cell apoptosis 3. KLB also contributes to transcriptional repression of CYP7A1, the rate-limiting enzyme in bile acid synthesis [UniProt]. Dysregulation of KLB is implicated in disease pathogenesis; patients with idiopathic pulmonary fibrosis exhibit decreased plasma KLB levels 3, and KLB targeting represents a promising therapeutic approach for managing metabolic and fibrotic diseases.