The FNIP1/FNIP2/folliculin complex helps maintain metabolic homeostasis during metabolic stress. (A) FNIP1 physically interacts with AMPK, FNIP2, and folliculin. In response to high AMP/low ATP, AMPK is phosphorylated and activated by LKB1 kinase. Activated AMPK then stimulates energy and nutrient production by increasing mitochondrial biogenesis, autophagy, and fatty acid oxidation, while inhibiting nutrient and energy consumption by mTOR. (B) FNIP1 deficiency in humans and mice results in metabolic imbalance and associated pathology. *As noted by Niehues et al.¹⁰