Labour’s deputy leader Tom Watson is stepping down from his role and will not run as an MP in the December election.
He says he will continue to campaign for the party, and the decision was “personal, not political”.
Labour leader Jeremy Corbyn thanked Mr Watson for his service, adding: “This is not the end of our work together.”
Mr Watson has often been at odds with the leadership and faced an attempt to oust him at Labour’s conference.
As an ardent Remainer, Mr Watson was also at odds with his own constituency, which voted 66% in favour of Leave at the 2016 referendum.
In his letter to Mr Corbyn, the former MP for West Bromwich thanked the leader “for the decency and courtesy you have shown me over the last four years, even in difficult times”.
He added: “Our many shared interests are less well known than our political differences, but I will continue to devote myself to the things we often talk about” – including gambling regulation, stopping press intrusion and campaigns on public health.
Mr Watson will not stand down until after 12 December vote, and said he would be “taking an active part in this election campaign”.
He also said that after the election, he “won’t be leaving politics altogether” – with plans to work on public health campaigns and release a book about his own struggle with Type 2 diabetes.
In his reply, Mr Corbyn said: “Few people have given as much to the Labour movement as you have and I know that many thousands of members and trade unionists you have inspired and worked with over the years will be very sorry to see you go.”
Mr Watson was elected deputy leader in 2015 on the same day that Mr Corbyn won his own ballot to run the party.
But the pair come from different political wings of Labour.
Mr Watson was a close ally of former Prime Minister Gordon Brown and worked in the top team of previous party leader Ed Miliband.
But Mr Corbyn was on the backbenches during this period and further left on the political spectrum than his deputy.
Since the pair have been running Labour, there have been a number of public disagreements, including most recently over the party’s Brexit position.
While Mr Corbyn has refused to say how he would campaign in a further referendum – as promised by the leader if Labour wins the election – Mr Watson has called for the party to “unequivocally back Remain”.
The day before the party’s conference in September, there was also an attempt to kick Mr Watson out of his post by the chief of the left wing campaign group Momentum, Jon Lansman.
However, the motion Mr Lansman tabled at a meeting of the National Executive Committee was dropped after Mr Corbyn intervened.
A number of former Labour MPs have paid tribute to Mr Watson.
London Mayor Sadiq Khan said his “energy, passion for politics and commitment to campaigning – whether fighting against Tory austerity or for better regulation of the gambling industry – will be much missed”.
Jess Phillips, who also represented a seat in the West Midlands before Parliament dissolved for the election, told the BBC: “It’s so very, very sad. I feel genuinely sad.
“I think the Labour Party needs to fight the election hard and then do some serious work to make sure we are the best we can be.”
The Jewish Labour Movement also called the decision “shocking and saddening”, saying he had been a “strong ally in the fight against anti-Semitism in the Labour Party”.