Making and breaking the inner nuclear membrane proteome.

The nuclear envelope (NE) is the defining feature of eukaryotic cells, separating the nucleus from the cytoplasm. It has a complex architecture consisting of two lipid bilayers that, despite being continuous between them and with the endoplasmic reticulum, have different protein compositions consistent with their distinct functions. In particular, the unique composition of the inner nuclear membrane (INM), facing the nucleoplasm and its underlying nuclear lamina, is critical for the organisation and function of nuclear processes, from cell fate to gene regulation and DNA repair. Mutations in INM proteins affecting this organisation are associated with muscular dystrophies and premature ageing syndromes highlighting the role of INM architecture in cell homeostasis. Here, we discuss recent progress in understanding how specific proteins concentrate at the INM, as well as the quality control mechanisms involved in remodelling and maintaining INM protein homeostasis.