FGF21 connects ER stress to sulfide signaling to enhance cellular resilience.

Fibroblast growth factor 21 (FGF21) is a stress-induced endocrine hormone that regulates metabolism. Grandl et al. show that FGF21, through its receptor β-klotho (KLB), enhances sulfide signaling and hydrogen sulfide production, strengthening the unfolded protein response and integrated stress response to promote stress resilience, metabolic adaptation, and potentially healthy aging.