Seipin: harvesting fat and keeping adipocytes healthy

Seipin is a key protein in the assembly of cytoplasmic lipid droplets (cLDs) and their maintenance at endoplasmic reticulum (ER)–LD junctions; the absence of seipin results in generalized lipodystrophy. How seipin mediates LD dynamics and prevents lipodystrophy are not well understood. New evidence suggests that seipin attracts triglyceride monomers from the ER to sites of droplet formation. By contrast, seipin may not be directly involved in the assembly of nuclear LDs and may actually suppress their formation at a distance. Seipin promotes adipogenesis, but lipodystrophy may also involve postadipogenic effects. We hypothesize that among these are a cycle of runaway lipolysis and lipotoxicity caused by aberrant LDs, resulting in a depletion of fat stores and a failure of adipose and other cells to thrive.