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It is always dangerous to venture an opinion as to why a problem is hard (cf. Clarke’s first law), but I’m going to stick my neck out on this one, because (a) it seems that there has been a lot of effort expended on this problem recently, sometimes perhaps without full awareness of the main difficulties, and (b) I would love to be proved wrong on this opinion :-) .
The global regularity problem for Navier-Stokes is of course a Clay Millennium Prize problem and it would be redundant to describe it again here. I will note, however, that it asks for existence of global smooth solutions to a Cauchy problem for a nonlinear PDE. There are countless other global regularity results of this type for many (but certainly not all) other nonlinear PDE; for instance, global regularity is known for Navier-Stokes in two spatial dimensions rather than three (this result essentially dates all the way back to Leray’s thesis in 1933!). Why is the three-dimensional Navier-Stokes global regularity problem considered so hard, when global regularity for so many other equations is easy, or at least achievable?
(For this post, I am only considering the global regularity problem for Navier-Stokes, from a purely mathematical viewpoint, and in the precise formulation given by the Clay Institute; I will not discuss at all the question as to what implications a rigorous solution (either positive or negative) to this problem would have for physics, computational fluid dynamics, or other disciplines, as these are beyond my area of expertise. But if anyone qualified in these fields wants to make a comment along these lines, by all means do so.)