Following mRNA translation in the cytosol, the three RAS isoforms (HRAS, NRAS and KRAS) are trafficked to the PM in a series of steps in specific subcellular localizations. HRAS and NRAS are recycled through palmitoylation-depalmitoylation cycles; KRAS is recycled via the recycling endosome which is enriched with PtdSer. Green and red lines indicate farnesyl and palmitate, respectively. The (+) symbol denotes polybasic residues of the KRAS hypervariable region. FTase, farnesyl transferase; RCE, Ras-converting enzyme 1 protease; ICMT, isoprenylcysteine carboxylmethyltransferase; PAT, palmitoyl acyl transferase; APT, acyl-protein thioesterase; PDEδ, phosphodiesterase delta; Arl2, ADP-ribosylation factor-like protein 2; ER, endoplasmic reticulum; Golgi, Golgi apparatus; RE, recycling endosome; PM, plasma membrane; -Me, methyl group.