CNKSR1 (connector enhancer of kinase suppressor of Ras 1) functions as a scaffolding protein that regulates multiple signaling pathways critical for cellular development and cancer progression. The protein serves as a scaffold component for receptor tyrosine kinases in MAPK cascades and interacts with proteins involved in intellectual disability through MAPK signaling 1. CNKSR1 demonstrates exclusive binding with RhoB-GTP, which regulates EGFR phosphatase activity by controlling the interaction between CNKSR1 and protein tyrosine phosphatase PTPRH at the plasma membrane 2. In cancer contexts, CNKSR1 mediates resistance to MEK inhibition by translocating to the plasma membrane where it stabilizes phosphorylated AKT, promoting crosstalk between MAPK and AKT signaling pathways 3. CNKSR1 also interacts with MAP4K kinases and can be displaced by SAMD12, affecting neuronal synapse development 4. Clinically, CNKSR1 mutations cause syndromic autosomal recessive intellectual disability with brain developmental defects 15. The protein's expression levels correlate with treatment responses in various cancers, including pancreatic and bladder cancers, suggesting potential as a biomarker for precision medicine approaches 36.