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Mailer, who moved to Ibrox in April 2025, was a key figure at the club, working with Patrick Stewart and Jim Gillespie under the new American ownership, led by chairman Andrew Cavenagh.
His exit comes amid a period of restructuring following Mr Gillespie's appointment as chief executive officer last season.
Staff, according to the Rangers Review, were informed of Mailer’s departure on Monday.
In a letter to staff, chief executive Gillespie said: "Greig has been an outstanding ambassador for the club during his time with us and he has made a significant contribution, both to the departments he has led, and to the wider leadership team, of which he has been a trusted and valued member.
"He has demonstrated strong leadership in everything he has done and has played a significant role in driving the club forward during a period of change.
"We will all miss his professionalism, work ethic, friendship, and support."
Gillespie cited Mailer's family caring responsibilities in England as incompatible with the club's requirement for a full-time presence in Glasgow.
He added: "I would like to thank Greig for his support, trust, and wise counsel, particularly over recent months, it has been greatly appreciated.
"I am sure everyone will join me in wishing him and his family every success in the future and he will always be very welcome back at Ibrox."
Mailer, who moved to the position of chief operations and communications officer in June, was previously the chief communications and marketing officer following his move from Brentford.
He spent three-and-a-half years at the Premier League club and also worked as corporate communications manager at Manchester United.
He was previously on the staff at Hibernian and oversaw the Scottish FA communications team from July 2017 to May 2019 after nearly seven years working at UEFA.
Mailer was one of the driving forces behind the creation of the Rangers Fan Advisory Board.