Aquaporin-0 (AQP0) is a tetrameric membrane protein and the most abundant membrane protein in the eye lens. Interestingly, there is little to no cellular turnover once mature lens fiber cells are formed, and hence, age-related modifications accumulate with time. While bottom-up mass spectrometry-based approaches can provide identification of post-translational modifications, they cannot provide information on how these modifications coexist in a single chain or complex. Native mass spectrometry, however, enables the transfer of the intact complex into the gas-phase allowing modifications to be identified at the tetramer level. Here, we present the use of native mass spectrometry and surface-induced dissociation to study the post-translational modifications of AQP0 isolated and purified from bovine eye lens, existing as multiple forms due to the different modification states naturally present.