Maintaining water balance in plant cells and organs involves control of water fluxes, and hence, a tight regulation of water channels (also called aquaporins) in plant cell membranes [1, 2]. In Arabidopsis, 35 homologs comprised in four homology subclasses have been identified. The plasma membrane intrinsic proteins (PIPs; with 13 isoforms further subdivided in the PIP1 and PIP2 subgroups) are the most abundant aquaporins in the plasma membrane. An excellent mechanism for fine-tuning the function of channels can be provided by post-translational modifications (PTMs). PTMs are central to regulate protein structure and function and thereby to modulate and control protein catalytic activity, subcellular localization, stability, and interaction with other partners. We showed that a short-term osmotic treatment induces a maximal root hydraulic conductivity inhibition by 60% that could be accounted for a decrease in PIPs function [3] and not in PIPs degradation since their cellular abundance remains stable [4]. By contrast, such treatment induced PIP2;1 internalization [5]. Using proteomics, we described PIPs as being modifiable by phosphorylation, acetylation, methylation, deamidation and ubiquitination [3, 4, 6, 7]. The MS quantification of phosphorylation and ubiquitination provided evidences for an interplay between phosphorylation and ubiquitination at the C-terminus of a major aquaporin (PIP2;1) [4]. We hypothesize that such interplay governs PIP2;1 internalization under osmotic stress. Perspectives will be discussed in terms of characterization of modifying enzymes involved in PIP2;1 internalization.