I think (on a subrational level) that there's some essence of personhood or consciousness that seems to transcend its material fabric, becoming more than the sum of its parts. "Transcend" is too strong a word, since by all appearances there's no static being that isn't still largely a result of and dependent on its makeup; as the foundation deteriorates so does the consciousness that results from it. That spectrum of functionality seems to undermine the possibility of a true soul that exists independent of its body.
But the word certainly signifies an actual thing, I think. Take a thought experiment: if we were to somehow make an exact replica of you, down to the molecular level, it would from all perspectives except your own be you. But the essence of what is you to yourself, your continuity of perspective, would (probably) not inhabit that new body, it would still inhabit your current one. The Star Trek / Prestige problem of conscious continuity suggests there's something there, at least conceptually.
The fact that there's still a lot about physics / the universe / consciousness that science doesn't understand leaves ample room for conjecture, for now.