How did Charles V respond to the Protestant Reformation?
Charles V, the Holy Roman Emperor at the time (1521), invited Martin Luther to the Diet of Worms (an assembly).
At first, Charles V referred to Luther's 95 theses as "an argument between monks" and maintained cordiality with Luther.
Later, Charles V would outlaw Luther and his followers, the Protestant Lutherans.
During periods of Protestant turmoil such as the 1524-1526 Peasant's Revolt and the 1531 formation of an alliance of Protestant German princes, Charles V delegated his power to his brother Ferdinand while he focused on other problems in the empire.
From Wikipedia: "In 1545, the opening of the Council of Trent began the Counter-Reformation, and Charles won to the Catholic cause some of the princes of the Holy Roman Empire. In 1546 (the year of Luther's natural death), he outlawed the Schmalkaldic League (which had occupied the territory of another prince). He drove the League's troops out of southern Germany and at the Battle of Mühlberg defeated John Frederick, Elector of Saxony and imprisoned Philip of Hesse in 1547. At the Augsburg Interim in 1548 he created an interim solution giving certain allowances to Protestants until the Council of Trent would restore unity. However, Protestants mostly resented the Interim and some actively opposed it. Protestant princes, in alliance with Henry II of France, rebelled against Charles in 1552, which caused Charles to retreat to the Netherlands."