Her father was John of Foix, Count of Étampes and Viscount of Narbonne, and her mother was Marie d’Orléans,[1] the sister of Louis XII of France.

[4] King Ferdinand II, Isabella's widower and Joanna's father, thus lost control of the countries that he had only ruled jure uxoris (Latin: "by right of [his] wife").

Their engagement was established on 12 October 1505, in 2nd Treaty of Blois, in which Louis XII ceded his claims to the Kingdoms of Naples and Jerusalem to his niece, provided that she had a son from the marriage.

[2] The marriage led to a short period of peace between France and Aragon,[8] but was badly received in Castile, where the majority of people had previously supported Ferdinand's claims, but saw his remarriage as a betrayal of their late queen, his first wife Isabella.

[2] Our [k]ing, if he does not rid himself of his appetites, will soon give his soul to the [C]reator and his body to the earth; he is already in the 63rd year of his life and does not allow his wife to separate from him and she is not enough for him, at least in his desire.Ferdinand's son-in-law, Philip, had died on 25 September 1506.

In his will he left Germaine Syracuse, Sicily, the towns of Tàrrega, Sabadell and Villagrasa in Catalonia, and Basilicata in Naples,[2] and ordered his grandson Archduke Charles to take care of her.

[2] Charles, Queen Joanna's son who had been raised in the Habsburg Netherlands,[14] arrived in Castile in 1517, and Germaine moved from Aragon to be closer to his court, and lived in the Monastery of El Abrojo near Valladolid.

At first, her stepgrandson, only 12 years her junior, showed much respect for her, rising from his seat and uncovering his head if she entered the room and addressing her kneeling, but soon abandoned this courtesy.

[citation needed] While in Barcelona, Charles arranged a marriage for Germaine with Margrave Johann of Brandenburg-Ansbach, Viceroy of Valencia, a landless cadet of the House of Hohenzollern.

[citation needed] This was the opposite of the more lenient approach of her predecessor, Diego Hurtado de Mendoza, Count of Melito and Lemus (1469–1536), who had worked for reconciliation.

[citation needed] In December 1524, Germaine signed a pardon that officially ended the persecution of all agermanats, but fines imposed on guilds and guild-aligned cities would take many years to pay.

[2] Germaine remarried a year later, in August 1526 in Seville to Ferdinand, Duke of Calabria (1488–1550), the eldest son of Frederick IV, the deposed king of Naples.

[2] In her will, Germaine de Foix included a major legacy:[16][17] Item, we bequeath and leave the string of 133 large pearls, which is the best that we possess, to the Most Serene Infanta Isabel of Castile, daughter of His Majesty the emperor, my son and my lord, on account of the great love that we feel for His Highness.A few days after Germaine's death, Duke Calabria sent a copy of the will to Empress Isabella with a cover letter noting "that Your Majesty can see the bequest of pearls that she left to the Most Serene Infanta.

"[16] In 1998, Jaime Salazar used the will and cover letter to suggest the possibility that Infanta Isabel of Castile was the daughter of Germaine and Charles V. Historian Manuel Fernández Álvarez agreed with this interpretation[18] but did not provide any further evidence.