RETSAT (retinol saturase) is an endoplasmic reticulum-localized oxidoreductase that catalyzes the saturation of all-trans-retinol to all-trans-13,14-dihydroretinol 1. Beyond this canonical enzymatic function, RETSAT regulates multiple biological processes through retinoid-independent mechanisms. In hepatic metabolism, RETSAT coordinates lipogenesis by regulating ChR2 activity upstream of glucose sensing, independent of its retinol conversion activity 2. RETSAT expression is upregulated under hypoxia via HIF-1α signaling and promotes replication fork restarting through interaction with DDX39B helicase, mediating gemcitabine resistance in pancreatic cancer 3. In ferroptosis regulation, RETSAT converts the ferroptosis-suppressive retinol into the weaker inhibitor 13,14-dihydroretinol, thereby promoting ferroptosis in cancer cells 4. RETSAT is essential for chromosome 2 in pluripotent stem cells, where it localizes to mitotic chr2 and interacts with cohesin/condensin components 5. In adipose tissue, RETSAT is regulated by β-adrenergic signaling and modulates cold-induced thermogenesis and lipolysis 6. Intestinal RETSAT expression is upregulated by high-fat diet and involved in obesity development and epithelial homeostasis 7. These diverse functions suggest RETSAT as a pleiotropic regulator relevant to metabolic disease, cancer, and inflammatory pathology.