SHOC2 is a leucine-rich repeat scaffold protein that serves as the core component of the SHOC2-MRAS-PP1C (SMP) holophosphatase complex, a critical regulator of the MAPK signaling pathway 1. The complex functions by selectively dephosphorylating inhibitory phosphorylation sites on RAF family kinases—specifically Ser-259 on RAF1, Ser-365 on BRAF, and Ser-214 on ARAF—thereby activating their kinase activity and potentiating MAPK signaling 1. SHOC2 binds both PP1C and GTP-loaded MRAS through its concave leucine-rich repeat surface, with initial complex assembly mediated by SHOC2-PP1C interactions and stabilized by MRAS binding 1. In cancer, SHOC2 represents a pharmacologically actionable dependency in RAS(Q61*)-mutant tumors, forming direct interactions with oncogenic NRAS that can be disrupted by small-molecule inhibitors to suppress MAPK signaling and cancer cell proliferation 2. SHOC2 mutations are associated with Noonan syndrome-like disorder with loose anagen hair, a RASopathy caused by gain-of-function variants that enhance holophosphatase activity 1. Additionally, SHOC2 activity contributes to acquired resistance in KRAS G12C-mutant cancers treated with targeted inhibitors 3, making it a relevant therapeutic target in both developmental disorders and cancer contexts 4.