Hypoxia-inducible lipid droplet-associated protein (HILPDA) (HILPDA)

Hypoxia-inducible lipid droplet-associated protein (HILPDA), also widely known as HIG2, is a small ~7-kDa protein that acts as a key metabolic regulator in response to hypoxia and nutrient stress. Primarily localized to the surface of lipid droplets and the endoplasmic reticulum, HILPDA serves as a direct inhibitor of adipose triglyceride lipase (ATGL), thereby blocking intracellular lipolysis and promoting the accumulation of neutral lipids. This metabolic reprogramming is a hallmark of many solid tumors, particularly clear cell renal cell carcinoma, where HILPDA expression is driven by hypoxia-inducible factors like HIF-1α and HIF-2α. Beyond its role in lipid storage, HILPDA has been implicated as an autocrine growth factor that enhances oncogenic Wnt signaling and contributes to tumor immune evasion by inhibiting natural killer cell activity. Therapeutically, HILPDA is considered a highly specific target for oncology, as its inhibition can trigger lethal lipid peroxidation and oxidative stress in cancer cells while its expression remains minimal in most normal adult tissues.

Other names

Hypoxia-inducible gene 2HIG2C7orf68HIG-2Hypoxia-inducible protein 2Hypoxia-inducible lipid droplet-associated protein