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How did the Medici family lose power in Florence again in 1527?

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A family tree diagram of the Medici family showing three branches: the minor branch, the principate, and the grand duchy, with names and dates for key family members organized in labeled sections.
Medici family

In 1527, the Medici family lost power in Florence as a direct consequence of the political instability caused by the Sack of Rome.1

During this period, the Medici Pope Clement VII had aligned himself with France against the Holy Roman Emperor Charles V as part of the League of Cognac. In May 1527, a riotous, largely unpaid imperial army marched on Rome and sacked the city, forcing the pope to take refuge in the Castel Santā€™Angelo.2

Taking advantage of this moment of weakness and the resulting chaos, republican factions in Florence rose up and expelled the Medici from the city. This republican government persisted until 1530, when the Medici were eventually restored to power following the reconciliation of the pope and the emperor.1