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Isabella I of Castile (22 April 1451 – 26 November 1504), born Ysabel, was the Queen of Castile and Léon. After Muhammad XII, an enemy of Isabella and her husband, retreated from Spain, she thanked Ezio Auditore da Firenze, who was responsible for the deed with the help of his fellow Assassins Luis Santangel, Isabella's advisor, and Raphael Sanchez, the financial minister. Ezio asked her if she would agree to Christoffa Corombo's plans to sail west and finance the journey, which she declined and responded to that the king of France had agreed to the plans. Luis and Ezio both realized that it was a plan set up by the Templars and Ezio hurried to Christoffa. Unbeknownst to Ezio at the time, Isabella was a Templar, or was, at the very least, greatly influenced by them.
Luis Santangel died, so Ezio sent someone to look for his journal. They discovered that Luis was trying to poison the queen presumably in revenge for the inquisition in which his family was prosecuted for being Jewish. In 1504, Ezio sent his apprentices to poison her with the same toxin that Luis attempt to use.