FNIP1 genetic variants linked to favorable metabolism in a million people
A large exome-sequencing study of 1,032,116 individuals uncovers rare FNIP1 coding variants associated with a favorable energy-metabolism state, measured by the triglyceride-to-HDL ratio. Follow-up experiments in human hepatocytes and mouse liver suggest that perturbing the FNIP–FLCN pathway enhances mitochondrial and lysosomal function and lipid catabolism, with downstream effects on insulin sensitivity and liver fat, offering mechanistic insight into genetic influences on cardiometabolic risk and liver–adipose communication.