There are infinitely many causes of equine lameness, including (but not limited to) disease and injury.
Common causes of lameness are broken bones, sprains/ strains, old injuries that never healed, or hoof problems.
A lame horse may have pain, which causes a "limp" or an uneven rhythm to their gait, or the lameness may be purely mechanical. This means that the horse does not have pain, but there is something causing physical limitation to the horse's gait-- such as an old muscle that healed too tight.
Some issues that cause lameness are quite fixable. Other causes, unfortunately, are not.