Twisting an ankle doesn't always happen on a run. Any single-leg exercise poses a risk. The ankle is a very mobile joint, but when the foot turns inward and the joint rolls too far, it can tear the ligaments that are on the outside of the ankle.
Running on a treadmill can especially put you at risk for a sprain as you may lose your focus and place one foot on the side and one foot on the belt while it's still in motion. Runners who prefer the outdoors aren't immune either--running over uneven terrain or stepping off and on curbs can increase your risk of a sprain.
How to prevent it: Reduce your risk for a sprain by performing ankle flexibility exercises and work on strengthening the muscles in the lower leg and foot. When running on a treadmill, exercise caution in getting on and off the belt and, if available, attach the safety clip that shuts the machine off if you fall. When running outdoors, aim for flatter, level surfaces and keep a close eye on foot placement when you run over challenging terrain.