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The Sun moves with respect to the local interstellar medium (LISM) and modifies its properties to heliocentric distances as large as 1 pc. The solar wind (SW) is affected by penetration of the LISM neutral particles, especially H and He atoms. Charge exchange between the LISM atoms and SW ions creates pickup ions (PUIs) and secondary neutral atoms that can propagate deep into the LISM. Neutral atoms measured at 1 au can provide us with valuable information on the properties of pristine LISM. New Horizons provides us with unique measurements of pickup ions in the SW region where they are thermodynamically dominant. Voyager 1 and 2 spacecraft perform in-situ measurements of the LISM perturbed by the presence of the heliosphere and relate them to the unperturbed region. The Interstellar Boundary Explorer (IBEX) makes it possible identify the 3-D structure of the heliospheric interface. We outline the main challenges in the physics of the SW–LISM interaction. The physical processes that require a focused attention of the heliospheric community are discussed from the theoretical perspective and space missions necessary for their investigation. We emphasize the importance of data-driven simulations, which are necessary for the interpretation and explanation of spacecraft data.more » « less
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