This five part limited series is of course part of the giant House of M alternate universe extravaganza. Spider-Man in this world is a hugely popular celebrity, who suffers a dramatic reversal of fortunes when the news is leaked that he is not in fact a mutant. (Remember that in this universe, non-mutants are second-class citizens). The story is mostly independant from the main House of M plot-line, and of course it's alternate universe, so you could ignore it entirely. But it's actually pretty decent stuff, so maybe go check it out just to be sure.