The 37-year-old Spain great Casillas and Pepe, who will be 36 later this month, have played 268 Champions League games between them heading into Tuesday's last 16, first leg which will see their Porto side take on Roma at the Stadio Olimpico.
Casillas holds the outright record with 173 appearances in Europe's elite club competition, and the two players -- who share a bond that is evident on the field but also in their social media posts -- have each won the Champions League three times.
When Madrid won the trophy in Lisbon in 2014, the last winner's medal for Casillas -- he was also a winner in 2000 and 2002 -- was also the first for Pepe.
The defender won it again in 2016 and 2017 before spending 18 months at Besiktas.
He rejoined Porto -- Portuguese champions and current league leaders -- last month on a deal until 2021 after being released by the debt-laden Turkish giants.
Pepe was born in Brazil but moved to Portugal as a young player and first signed for Porto in 2004, spending three years there before a big-money move to Madrid in 2007.
"Porto are the club who prepared me for the demands of top-level football. I owe them a lot," said Pepe, who has gone on to win more than 100 caps for Portugal and was part of their Euro 2016-winning side.
He claims to have rejected more money elsewhere to go back to Portugal, where he was rewarded with a tax break of 50 percent on his income as part of a government measure to entice back people who left the country during the economic crisis.
His only stated aim has been to "share his experience", but Pepe immediately established himself in Sergio Conceicao's line-up, playing alongside the Brazilian Felipe in central defence.
That has been to the detriment of others, including the talented Brazilian Eder Militao, who had been linked with a move to Real and has now been shunted out to right-back.
Still going strong
Behind them, Casillas has only a few months left on his contract at the Estadio do Dragao, although he claims to want to stay "much longer" before ending a career that has also seen him win a World Cup and two European Championships with Spain.
The goalkeeper left Real in tears in 2015 but has kept going at the top level with Porto and is now in his 20th consecutive season playing in the Champions League.
"I feel extremely proud to have won (the competition) three times and managed to stay in the Champions League for so long," Casillas said in an interview with UEFA published on Saturday.
Porto have not made it past the last 16 since Casillas joined the club and he will be determined to erase the memory of last season, when the Dragons went out at this stage after being destroyed 5-0 at home by Liverpool in the first leg.
Casillas was dropped for that game, with Jose Sa -- now on loan at Olympiakos -- taking his place, but the Spaniard returned for the second leg at Anfield, which ended 0-0.
He will be there in Rome on Tuesday alongside Pepe, as Porto aim for a result that will set them up nicely for the return next month.