A flavour symmetry based on Z_4 is analysed in the context of SU(5) Grand Unification with the standard fermionic content plus three right-handed neutrinos. The role of Z_4 is to forbid some Yukawa couplings of up- and down-quarks to Higgs scalars such that the quark mass matrices M_u, M_d have Nearest-Neighbour-Interaction (NNI) structure, once they are generated through the electroweak symmetry breaking. It turns out in this framework that Z_4 is indeed the minimal discrete symmetry and its implementation requires the introduction of at least two Higgs quintets, which leads to a two Higgs doublet model at low energy scale. Due to the SU(5) unification, it is shown that the charged lepton mass matrix develops also NNI form. However, the effective neutrino mass matrix exhibits a non parallel pattern, in the framework of the type-I seesaw mechanism. Analysing all possible zero textures allowed by gauge-horizontal symmetry SU(5) x Z_4, it is seen that only two patterns are in agreement with the leptonic experimental data and they could be further distinguished by the light neutrino mass spectrum hierarchy. It is also demonstrated that Z_4 freezes out the possibility of proton decay through exchange of colour Higgs triplets at tree-level.