Overstimulation of host lipid metabolism by HCV during infection is achieved through a variety of molecular mechanisms (reviewed in [27] , [28] , and [29] ). For example, HCV employs multiple strategies to activate the sterol regulatory element binding protein (SREBP) pathway, which is important for regulation of host lipid homeostasis [19, [30] [31] [32] . SREBPs are endoplasmic reticulum (ER), membrane-anchored transcription factors that respond to changes in intracellular sterol levels through interactions with sterol-sensing proteins (reviewed in [33] ). When sterol levels are high, SREBPs are retained as inactive precursors in the ER [34, 35] . Under low sterol conditions, SREBPs are escorted to the Golgi, where two resident endoproteases (subtilisin kexin isozyme/site-1 protease (SKI-1/S1P) and SREBP Site-2 protease (S2P); reviewed in [36] and see below) cleave the precursor polypeptide SREBP, allowing the release of transcriptionally active SREBP molecules from the ER [37, 38] . The released SREBP fragment migrates to the nucleus and binds to sterol response elements in the promoters of cholesterol and fatty acid biosynthetic target genes, and it activates their transcription [39] [40] [41] . Activation of the SREBP pathway by HCV aids the virus lifecycle and may ultimately promote the development of steatosis and liver disease in chronically infected individuals [42, 43] .