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Elucidating the long-term history of the Greenland Ice Sheet (GrIS) is essential for understanding glacial instability thresholds, identified as major climate system tipping points, and how the cryosphere will respond to anthropogenic greenhouse gas emissions. To address current knowledge gaps in the evolution and variability of the GrIS and its role in Earth's climate system, International Ocean Discovery Program (IODP) Expedition 400 will obtain cores from seven sites across the northwest Greenland margin into Baffin Bay where thick Cenozoic sedimentary successions can be directly linked to the evolution of the northern GrIS (NGrIS). The strategy of drilling along this transect is to retrieve a composite stratigraphic succession representing the Late Cenozoic era from the Oligocene/Early Miocene to Holocene. The proposed sites will specifically target high–accumulation rate deposits associated with contourite drifts and potential interglacial deposits within a trough mouth fan system densely covered by seismic data. We seek to test if the NGrIS underwent near-complete deglaciations in the Pleistocene and to assess the ice sheet’s response to changes in orbital cyclicities through the mid-Pleistocene transition. Paleoclimate records will be obtained that can provide chronology on the NGrIS expansion and unravel potential linkages between marine heat transport through Baffin Bay and high Arctic warmth during the Pliocene. A deep coring site (980 meters below seafloor) targeting a Miocene and Oligocene strata succession will examine possible linkages between changes in atmospheric CO2 and climate-ecosystem conditions in Greenland. The overall aim is to investigate the full range of forcings and feedbacks—oceanic, atmospheric, orbital, and tectonic—that influence the GrIS over a range of timescales, as well as conditions prevailing at the time of glacial inception and deglacial to interglacial periods. The data and results gathered from Expedition 400 will effectively constrain predictive models addressing the GrIS response to global warming and its impending effects on global sea levels.