Within the RAS pathway, heterozygous mutations in signaling components (RRAS, RAC2, and SOS1) or RAS regulators (PLXNB2, ABI1, and PDE8A) have been described in JMML in combination with some of the classical driver events and contribute to JMML pathogenesis by enhancing RAS pathway activation (Table 1) [29,37,64]. Here, RAC2 is linked to juvenile myelomonocytic leukemia.