Of note, whereas activating Ras mutations are rare in HCC (Zucman-Rossi et al., 2015), alterations in the intensity of MAPK Erk signalling participate in shaping the tumoural phenotype, as revealed by inactivating mutations of Rsk2, which is both an ERK target and a negative regulator of the pathway (Chan et al., 2021). Here, RPS6KA3 is linked to hepatocellular carcinoma.