Conversation so far:
what was the name of the country Charles V, the Holy Roman Emperor, had the most issues with?
Much of Holy Roman Emperor Charles V's reign was taken up by conflicts with France, which found itself encircled by Charles's empire while it still maintained ambitions in Italy.
what year did Charles V, Holy Roman Emperor, have his conflict with his nemisis?
The first war with Charles V's great nemesis Francis I of France began in 1521.
did France concur Milan during Charles V's reign as holy roman emperor?
Holy Roman Emperor Charles V allied with England and Pope Leo X against the French and the Venetians, and was highly successful, driving the French out of Milan

Question: what year was the final war? Who was in it?
Self-contained rewrite: what year was the final war with France for Charles V, Holy Roman Emperor? Who was in it?