CPS1 and intrahepatic cholangiocarcinoma: In NSCLC and intrahepatic cholangiocarcinoma of the liver cancer, the mitochondrial urea cycle enzyme CPS1 was downregulated either directly (Figure 5, I and K) or via reduced expression of NAGS, the enzyme that produces its essential cofactor N-acetylglutamate, respectively (Figure 5, J and L, and Supplemental Figure 4B).