Given a symmetric operator on a domain of some Hilbert space, there may be several extensions of it to a self-adjoint operator. These typically correspond to choices of boundary conditions (WeiJiang).
In quantum mechanics the observables are supposed to be self-adjoint operators, in particular the Hamiltonian. The physical input often directly provides only a symmetric operator, which encodes local information about the dynamics of the system . The choice of its self-adjoint extension corresponds to choices of boundary conditions on the states of the system, hence global information about the kinematics .
See the References on applications in quantum mechanics below.
An exposition and motivation by means of the simple case of a quantum particle in an infinitely deep well potential is given in
A discussion in the context of AQFT is in
Applications to quantum field theory of anyons is discussed in