A sliding door system can include a tiltable sealing mechanism such that, when a door panel is slid to a closed configuration, one or more seal elements form a seal between the door panel and its surroundings at the top, bottom, and/or sides of the door to reduce or prevent infiltration or communication of gases or liquids such as air or water. Manual or motor driven movement of the panel can move an actuation mechanism to extend the seals around the door. The sealing member can include weather stripping, brush or another seal element for sealing contact with a header, floor, door, frame, or other surface. Multiple door panels can be arranged to form a door panel system.