The HCV RNA transcript encodes both structural and nonstructural HCV proteins. The untranslated regions (UTR) at the 5′ and 3′ ends are essential, as they contain sequence and structural elements that are critical for HCV translation and RNA replication. Initial HCV genome sequences did not include all of the 3′ UTR, and it was later shown that the 3′ X-tail of the HCV transcript is essential for viral production. HCV is translated as a polyprotein that contains both structural and nonstructural proteins. Subgenomic replicons containing the HCV replication machinery (gray bar) have been invaluable for studies of the HCV replication. The HCV polyprotein undergoes photolytic processing and is assembled in the host ER. Several HCV proteins have been explored as drug targets, including the viral RNA polymerase (NS5B). Sofosbuvir, which targets the viral RNA polymerase (NS5B), was approved by the FDA in 2013 and is associated with very high cure rates.