The resignation of David Frost is a major blow to Boris Johnson.
A long time confidant and advisor to Mr Johnson, he negotiated the Brexit Withdrawal Agreement, including the Northern Ireland Protocol in 2019, and the Trade and Co-operation Agreement with the EU the following year.
Earlier this year, Boris Johnson appointed him to the House of Lords, and made him a cabinet minister for relations with the EU.
His main task was to negotiate a radical change of the Northern Ireland Protocol and he set out his plans in a document in July.
Having been made by Boris Johnson, his resignation will be felt personally by the prime minister. It increases the possibility that Mr Johnson will face a leadership challenge soon and that in itself is a signal that Lord Frost may believe Mr Johnson may not survive that challenge.
The reported reasons for his resignation have been described as "full spectrum" - pretty much every major policy of the government – with the exception of Brexit. But all has not been well on that front either.
Last week, official briefings suggested the government was no longer seeking all of his sweeping changes for the protocol.
They include the removal of any role for the European Court of Justice, and the overall governance of the agreement: how the two sides would resolve disputes and manage divergence by the UK from existing EU rules and standards - and would simply concentrate on changes to ease the flow of goods into Northern Ireland.
Lord Frost pushed back against the briefings in the House of Lords on Thursday and in a statement on Friday announcing the talks with the EU will run on into next year.
He wrote: "Our preference would be to reach a comprehensive solution dealing with all the issues. However, given the gravity and urgency of the difficulties, we have been prepared to consider an interim agreement as a first step to deal with the most acute problems, including trade frictions, subsidy control, and governance.
"Such an agreement would still leave many underlying strains unresolved, for example those caused by diverging UK and EU rules over time.
"It would therefore be inherently provisional by nature and would accordingly need to include mechanisms for addressing outstanding issues and resolving new concerns as they arise."
He also reiterated his view that the conditions existed to use Article 16, the so-called safeguard clause in the Northern Ireland Protocol, which can be used to try to force changes to specific aspects of the protocol.
Early in the autumn – in September and October – there was a lot of noise in the British media suggesting Article 16 would be triggered. In a side meeting at the Conservative Party conference in October, the first question to David Frost was when was he going to use Article 16: this provoked cheering and sustained applause from the audience.
But as the month went on, the media drumbeat on Article 16 died away to nothing.
This coincided with the increasing troubles the prime minister and his government were facing:
- the sleaze scandal over paid lobbying
- the cost of the prime minister's flat refurbishment
- the revelations about Christmas parties in Downing Street this time last year, when the country was in lockdown
- the emergence of a video apparently showing Downing Street aides laughing and joking about a Christmas party
- the huge revolt by 100 Tory backbenchers against the governments anti-Covid measures on Tuesday
- the spectacular loss by the Conservatives in Thursday's by-election in North Shropshire;
- Friday night's debacle, when the cabinet secretary, who had been tasked by the prime minister with investigating the holding of Christmas parties in Downing Street, had to step down from the investigation when the SNP revealed he had attended a Christmas Party for his own staff.
The partygate investigation is now being run by Sue Grey, a tough and independent minded senior civil servant, who used to run the Department of Finance at Stormont. Whitehall commentators expect her to pull no punches in her report. When it emerges, it could have a big bearing on Mr Johnson's grip on power.
It was against this background of growing dissatisfaction with the prime minister, and claims that he is losing his grip on the government and the Conservative Party, that Saturday night's bombshell about Lord Frost's resignation became public.
The Mail on Sunday, which broke the news, reported that Lord Frost was dissatisfied with the direction the government was taking, particularly over its Covid lockdown measures (which he reportedly argued against at Cabinet), about recent tax rises (the UK has its highest tax burden since the 1950s), and the huge cost of measures to combat climate change.
In his resignation letter – sent to Downing street after the Mail broke the story – Lord Frost wrote: "You know my concerns about the current direction of travel. I hope we will move as fast as possible to where we need to get to: a lightly regulated, low tax, entrepreneurial economy."
With the main challenges in any leadership challenge to Boris Johnson expected to be Foreign Secretary Liz Truss, and Chancellor of the Exchequer Rishi Sunak, Lord Frost has indicated a preference for Mr Sunak's policy.
In a speech to the Institute of Economic Affairs (a conservative think tank) last month, Lord Frost said: "The formula for success as a country is well known - low taxes. I agree with the Chancellor, as he said in his budget speech, our goal must be to reduce taxes."
In the same speech, he also weighed in against Covid restrictions, saying: "I am very happy that Free Britain – or at least merry England, is probably now the freest country in the world as regards Covid restrictions. No mask rules, no vaccine passports – and long may it remain so."
Frost is very popular with Conservative Party activists: the regular tracking poll of satisfaction with government ministers run by the website Conservative Home has consistently rated Frost the second most admired cabinet minister, with most recent rating of 73%, second only to Liz Truss on 82%.
Rishi Sunak is on 53% - but the prime minister is on minus 17% (only his chief whip Mark Spencer has a lower rating with conservative activists - and these numbers pre-date the last fortnight of negative news).
With an immediate resignation of the lead Brexit minister, attention now turns to who will be appointed to this important role in the British government – and how will that person deal with the protocol talks.
At the end of a very bad week for Boris Johnson, this resignation will guarantee the bad news continues to flow into Christmas week.