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Angela Ahrendts, the former high fashion boss of Burberry brought in to revitalise Apple's retail stores, is stepping down after five years.
Apple said Ms Ahrendts will leave the company in April "for new personal and professional pursuits".
She is one of its highest paid executives, earning nearly twice as much as boss Tim Cook in 2017.
Ms Ahrendts will be replaced by Deirdre O'Brien, whose role as vice president of people will expand to cover retail.
During her time at Apple, Ms Ahrendts opened a number of flagship stores, aimed at creating a "community space" as opposed to just selling the firm's latest product.
Mr Cook said: "She has been a positive, transformative force, both for Apple's stores and the communities they serve. We all wish her the very best as she begins a new chapter."
Ms Ahrendts was previously chief executive of Burberry, where she oversaw its transformation from a British brand best-known for its checked raincoats to a leading name on the world's catwalks.
By the time she left in 2014, she was one of the FTSE 100's highest paid chief executives.
In 2017, Ms Ahrendts earned $24.2m, compared to Mr Cook who took home $12.8m.
Apple recently reported a sharp fall in revenue from its iPhone and hinted that it could lower prices to boost demand.
Overall, first quarter revenue fell by 5% to $84.3bn compared to the same period last year.