The nuclear lamina is a fibrous meshwork of proteins found adjacent to the inner 
nuclear membrane that plays a critical role in the maintenance of nuclear 
architecture. Made up of A and B type lamins, the nuclear lamina has recently 
been shown to contribute to numerous cellular functions such as chromatin 
organization, DNA replication, cellular proliferation, senescence, and aging. 
While at least a dozen disorders are associated with LMNA, the focus of this 
review is Autosomal Dominant Leukodystrophy (ADLD), the only disease associated 
with the lamin B1 gene (LMNB1). ADLD is a fatal, adult onset CNS demyelinating 
disorder that is caused by either genomic duplications involving LMNB1 or 
deletions upstream of the gene. Both mutation types result in increased LMNB1 
gene expression. How the increased levels of this widely expressed nuclear 
structural component results a phenotype as specific as demyelination is a great 
mystery. This review summarizes what is currently known about the disease and 
describes recent work using animal and cell culture models that have provided 
critical insights into ADLD pathological mechanisms. The delineation of these 
pathways provides a fascinating glimpse into entirely novel roles for the 
nuclear lamina and will be critical for the identification of therapies for this 
fatal disease.