Underlying health issue. Diabetes, urinary tract infection, etc.
Other things to consider:
Has there been a change in the house like the addition of a new animal?
Did you change the type of litter?
Did you move the box?
Are you diligent in scooping daily?
Is there something new near the box that would make it unappealing?
One other question. Is the cat going near the box or other places?