The marriage of proteomics with cell biology has produced extensive inventories of the proteins that inhabit several subcellular organelles. Recent proteomic analysis has identified many new putative transmembrane proteins in the nuclear envelope, and transcriptome profiling suggests that the nuclear-membrane proteome exhibits some significant variations among different tissues. Cell-type-specific differences in the composition of protein sub-complexes of the nuclear envelope, particularly those containing the disease-associated protein lamin A, could yield distinctive functions and, thus, explain the tissue specificity of a diverse group of nuclear-envelope-linked disorders in humans. Considered together, these recent results suggest an unexpected functional complexity at the nuclear envelope.