Before the discovery of Sotorasib, efforts on directly targeting KRAS mutation have historically achieved little success due to the complexity associated with KRAS mutations . Since KRAS interacts with several proteins and are involved in many regulatory processes, including cell growth and differentiation , the inhibition of specific upstream or downstream signaling pathways, membrane localization and protein interactions, can provide Targeting PDE6D for inhibiting KRAS: A computational approach an alternative pathway for discovering effective inhibitors for treating KRAS mutation lung cancer. An important protein that KRAS interact with is phosphodiesterase 6δ (PDE6D)termed the trafficking chaperone of prenylated proteins . Phosphodiesterase 6δ (PDE6D) has a beta-sandwich immunoglobulin fold which contains a hydrophobic pocket capable of binding to the farnesyl group . showed that PDE6D binds to and sequesters the lipid of cytoplasmic RAS. Also, Zimmermann et al. showed that the manipulation of PDE6D directly affects the localization and spatial organization of KRAS, which had implication on RAS signaling. Since targeting KRAS directly might appear elusive, a focus on the KRAS: PDE6D complex by targeting PDE6D can be an effective approach towards developing drug candidates that could treat KRAS-mutation-associated lung cancer. Moreover, there have been reports on indirect inhibitor discovery against PDE6D .