KSR1 is a scaffolding protein that positively regulates the Ras/Raf/MEK/ERK signaling cascade, a central pathway controlling cell proliferation, survival, and differentiation. Rather than functioning primarily as an active kinase, KSR1 acts as a platform that assembles signaling complexes, particularly by binding to MEK1/MEK2 and promoting BRAF-mediated phosphorylation of these kinases independent of KSR1's own catalytic activity. KSR1 undergoes phosphorylation-dependent translocation from the cytoplasm to the cell membrane in response to growth factor stimulation, facilitating interaction with activated Ras and Raf proteins. Its kinase activity remains controversial—while some evidence suggests EGF treatment can enhance KSR1 kinase activity in certain contexts, the physiological significance remains uncertain. KSR1 is aberrantly overexpressed and functionally critical in multiple cancer types. In colorectal carcinoma, KSR1 promotes tumor cell survival by regulating Myc and PGC1β expression 1. In small cell lung carcinoma, KSR1 regulates tumor-initiating cell formation and mediates cisplatin resistance; notably, KSR1 knockout prevents chemotherapy resistance in over 90% of SCLC cells across multiple subtypes 2. KSR1 also promotes fibrosis in intrauterine adhesions via the MEK/ERK pathway 3. These findings suggest KSR1 inhibition as a potential therapeutic strategy in cancers dependent on aberrant Ras/Raf/MEK/ERK signaling.