Seipin: a mysterious protein

In 2001, a locus for autosomal-recessive congenital generalized lipodystrophy was identified on chromosome 11q13 and mutations in a novel gene named Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) were reported. Earlier this year, heterozygous mutations in the BSCL2 gene, restricted to the N-glycosylation (N-X-S/T) motif, were reported in autosomal-dominant distal hereditary motor neuropathy and Silver syndrome, which are disorders with distinctly different phenotypes from lipodystrophy. BSCL2 encodes seipin, a transmembrane protein that is localized to the endoplasmic reticulum. It is proposed that its homology to midasin, an AAA (ATPases associated with various cellular activities) domain-containing nuclear protein that is involved in RNA transport, might yield some clues as to how mutant forms of seipin cause two clinically distinct syndromes.