Some questions, if answered, could drastically change our beliefs about what is best to focus on. Orienting your research toward answers to these questions -- also known as crucial considerations -- could have profound impact compared to other possible research agendas.
If you would like to get a better sense of what is meant by a "crucial consideration," listen to this extended presentation on the topic. You can also read the Crucial Considerations blog of the Foundational Research Institute, including their list of open research questions. For people who believe we should prioritize existential risk reduction, Convergence Analysis is in the process of mapping “cruxes” and writing associated literature reviews.