In eukaryotes, the nucleus is confined by the nuclear envelope that consists of two membrane layers, the outer nuclear membrane (ONM) and the inner nuclear membrane (INM), which contains a number of proteins that are involved in nuclear processes. However, the fate of these INM integral proteins is unclear, and it is not known whether they are stable throughout the organismal lifetime, as has been shown for some nucleoporins, or are degraded. On page 3603, Roland Foisner and colleagues now investigate the turnover of Asi2, an integral INM protein in Saccharomyces cerevisiae. They find that Asi2 is ubiquitylated and subsequently degraded by the proteasome in a manner that is dependent on Doa10, an ER-associated E3 ubiquitin ligase known to also partially localise to the INM. In addition, as shown here, Asi2 degradation also requires the E2 enzymes Ubc6 and Ubc7 that have previously been shown to be necessary for Doa10 function. Furthermore, the authors demonstrate that nuclear proteasomes are responsible for Asi2 degradation, as the protein is stabilised in sts1-2 mutants that exhibit impaired nuclear accumulation of proteasomes. Moreover, mutants with a deletion of the ubiquitin ligase Hrd1, which is required for degradation in the ER, do not exhibit Asi2 degradation defects. Taken together, these data provide the first evidence for proteasome-mediated turnover of integral membrane proteins in the nucleus, which might have implications for diseases associated with aberrant nuclear envelope protein levels.