Spoilers follow...
I'm almost done with House of Leaves, and so far I agree it's totally mind blowing.
I'd like to throw out my theory on it and see what you all think...
My take on it is that the whole thing is the descent in to madness (schizophrenia/ possibly manic depressive) of "Johnny Truant". In the beginning, in places where you read Johnny's notes, you can see him occasionally slip into the kind of 'stream of consciousness' writing that you also find in his mother's letters- any time he starts to delve into the realm of his own emotions.
I also believe that the House, Zampano, the Navidson/ Green family and associated friends (there were times that I thought that Chad may actually be Johnny), and all the associated professional interviewees and footnotes were just manifestations of Johnny slipping into the dark labyrinth of his troubled mind (the need for order through extensive lists. Reminds me of 'A Beautiful Mind'.). Karen, beautiful- just like Johnny's mother, Navy- brave, the 'saviour' as Johnny's father had saved him from his mother's insanity. Tom- nice guy/ looser not unlike the outward perception of Johnny. References that Johnny makes about the beauty of a woman's wrists, later to learn that Johnny remembers specifically his mother's wrists before his father took her away.
Also there is the duality of his final journaling- the evil, dark, murderous, blood filled memories- the barely contained rage balanced by the maybe true/ maybe false story about his doctor friends in Seattle. While both stories maybe totally false, I feel they highlight the duality of his mind when in the throes of his illness (not unlike that of his mother) reflected through his writing. Which is true? Maybe neither... and as he points out extensively... what does it matter in the end? Especially in light of the photographed note in Appendix B "Perhaps I will alter the whole thing. Kill both children..."
I could go on and on... Jonah and the Whale/ His mother in the Whale, her encoded letter/ his encoded foot notes, the husky Johnny met up with in the park (Hillary), the references of rust when he talks of the dark (leading back to his memories of the sinking ship), a possible connection between the Haitian of his ship and Delial (this maybe something I'm just reading into it, but I could never quite grasp why the Haitian was so important until the story of Delial came to light), the five and a half minutes it took Johnny's father to get his mother out of the house/ the five and a half minute hallway.
I keep adding to this, sorry.
To me there is no house, no Zampano, no murdered Kyrie, just a lost, damaged and tragically brilliant man trying to break the hold of his mother's illness over his life and his mind. I think that Zampano is the character Johnny uses to tell the story of a family trying to stay together, a make-believe story that Johnny wants to be real, to prove that a family can stay together and be happy, unlike his. Unfortunately, he could not keep his demons out of their lives, and though they overcame his monstrous trials in the end, I don't know if Johnny is really sure the same will hold true for himself.
So, there. My two cents.