En is the sixth inheritor, whereas Nana is the seventh inheritor of one of the most powerful quirks in My Hero Academia, One for All. En passed on his powers to Nana after a death battle against the main antagonist of the series, All for One.
As they are the consecutive inheritors of One for All, many have wondered whether they are related more closely than just by quirk powers. En's special ability besides the One for All quirk was a smokescreen, which allowed him to spread a purple smoke around him that blinds his enemies for a while.
Nana's special ability apart from One for All was her float ability, which allowed her to float mid-air. This ability was not only seen in Izuku, but also in All Might throughout his career.
Disclaimer: This article contains potential spoilers from the My Hero Academia manga series.
Exploring the relationship between En and Nana Shimura from My Hero Academia
Although the relationship between En and Nana Shimura hasn't been revealed officially, fans speculate them to be siblings. This relationship hasn't been teased in any way in the anime or manga series of My Hero Academia, so far.
En was already a pro hero during his time before he inherited One for All. He got the powers of One for All from the current inheritor of One for All, Daigoro Banjo, (the fifth inheritor of One for All) who was gravely injured after fighting All for One.
During his last moments, Daigoro passed on his blood to En as a way to transfer his powers of One for All to him, before being killed by All for One. This made En the sixth inheritor of One for All.
Later in his life, En met Nana Shimura, who was also a pro hero before inheriting the power of One for All. As the person who desired One for All the most, All for One eventually found the whereabouts of En and started hunting him down.
During his last moments, En was lucky enough to pass on One for All to Nana through his hair (just like how All Might passed One for All to Izuku Midoriya), before being killed by All for One.
As Nana already had a muscular body, she was able to withstand One for All and became the seventh inheritor of One for All. This led the fans of My Hero Academia to think that these two might have been long-lost siblings who didn't know about each other.
Final thoughts
As My Hero Academia is reaching its final chapters, fans are speculating that it might be pretty unlikely that Kohei Horikoshi (the author of My Hero Academia) will reveal the origins of each One for All inheritor. What he has revealed so far was necessary to carry the story forward, but revealing each inheritor's origin individually might take some chapters to explain.
The author could release a separate manga series, just like My Hero Academia: All Might Rising, in which he gives a basic overview of the past of each inheritor of One for All. However, as there is no official confirmation about this, it is advised that one takes this information with a grain of salt.