LEM-domain proteins present a growing family of nonrelated inner nuclear membrane and intranuclear proteins, including emerin, MAN1, LEM2, several alternatively spliced isoforms of LAP2, and various uncharacterized proteins in higher eukaryotes as well as the Drosophila-specific proteins otefin and Bocksbeutel. LEM-domain proteins are involved in diverse cellular processes including replication and cell cycle control, chromatin organization and nuclear assembly, the regulation of gene expression and signaling pathways, as well as retroviral infection. Genetic analyses in different model organisms reveal new insights into the various functions of LEM-domain proteins, lamins, and their involvement in laminopathic diseases. All these findings as well as previously proposed ideas and models have been summarized to broaden our view of this exciting protein family.