The decision by Boris Johnson's brother to resign from the government has been a particularly heavy blow for the British prime minister, leaving him in a minority within his own family as well as the country's parliament.
Jo Johnson stepped down on Thursday, saying he could no longer reconcile family loyalties and the national interest.
It rounded off a humiliating week for Johnson in which MPs tore up his hardline Brexit strategy in a series of votes.
He told the BBC he was "very sad" at the news but tried to play it down saying: "Jo and I haven't seen eye-to-eye for a long time about the UK and the European Union".
In a rambling performance at a press event in Yorkshire later on Thursday, he said Brexit was "an issue that obviously divides families and divides everybody".
Jo Johnson, a former investment banker married to a journalist from the left-wing Guardian newspaper, had already resigned from government under Johnson's predecessor Theresa May to call for a second referendum.
That left commentators puzzled when, just months later, he joined his brother's strongly pro-Brexit government.
Brexit has caused severe rifts within many families in Britain ever since the 2016 referendum - most often been an older pro-Brexit generation and a younger pro-EU one.
That dynamic is reversed in the case of the Johnsons, a highly political family, where the father Stanley has been a strong supporter of staying in the European Union.
A third sibling, Rachel, is also anti-Brexit.
The views of the fourth sibling, Leo, are unknown as he has distanced himself from politics, building a career in the City and as a co-host of a BBC radio series exploring how innovation can transform the way society functions.
Some of Leo's retweets have raised suspicions, however, including of a comment referring to Brexiteers as "holier than thou so-called upholders of democracy".
Stanley worked for the European Commission in the 1970s and then served as a Conservative MEP, while Rachel ran unsuccessfully for the European Parliament in elections this year for the anti-Brexit Change UK party.
After the news of Jo's resignation, Rachel tweeted to say that "the family avoids the topic of Brexit, especially at meals, as we don't want to gang up on the PM!"
The resignation came after 22 MPs left the governing Conservative party this week in protest against the government's decision to leave the EU on October 31, come what may.
The opposition Labour party seized on his departure.
Deputy leader Tom Watson tweeted: "Once again, the people who trust Boris Johnson least are the ones who know him best."
Pollster Joe Twyman tweeted: "It's going to be a hell of a Christmas lunch in the Johnson household".
BBC journalist David Cornock quipped: "A rare case of a politician resigning to spend less time with his family".
Friday's newspapers devoted plenty of column inches to the sibling rivalry.
The Daily Mail ran a headline reading "Et Tu, Jo?", while The Metro front page said "BoJo blow as bro Jo goes".