HSD17B13 encodes hydroxysteroid 17-beta dehydrogenase 13, a lipid droplet-associated protein with significant roles in hepatic lipid metabolism and liver disease susceptibility. The protein localizes to lipid droplets and facilitates dynamic organelle communication between lipid droplets and the Golgi apparatus through interaction with Rab2A, contributing to very-low-density lipoprotein (VLDL) lipidation and secretion 1. HSD17B13 is transcriptionally regulated by the circadian clock protein BMAL1 and mediates hepatocyte autophagy, playing a crucial role in circadian control of hepatic ischemia/reperfusion injury 2. A loss-of-function splice variant (rs72613567:TA) in HSD17B13 provides significant protection against chr4 liver disease, reducing risk of alcoholic liver disease by up to 53%, nonalcoholic liver disease by up to 30%, and various forms of cirrhosis 3. This protective variant is associated with reduced progression from hepatic steatosis to steatohepatitis and can mitigate liver injury associated with the PNPLA3 risk allele 3. The gene represents a major genetic risk factor for NAFLD-associated hepatocellular carcinoma 4 and is being actively pursued as a therapeutic target through oligonucleotide-based therapies for metabolic dysfunction-associated steatotic liver disease 5.