Lipid droplet biogenesis-associated protein seipin (BSCL2)

Lipid droplet biogenesis-associated protein seipin (BSCL2) is a homo-oligomeric integral membrane protein of the endoplasmic reticulum that concentrates at junctions with cytoplasmic lipid droplets. It is essential for normal adipocyte development and function, controlling the assembly and maintenance of lipid droplets, crucial for energy storage and metabolic balance. Loss of seipin function—almost always through pathogenic variants in the BSCL2 gene—leads to severe, early-onset generalized lipodystrophy, marked by a near-complete absence of adipose tissue and metabolic complications such as insulin resistance, diabetes, and fatty liver. Distinct mutations can also cause motor neuronopathies and encephalopathies, underlying the protein’s critical but tissue-specific role in neuronal health. Seipin’s precise molecular mechanisms remain incompletely understood, but it acts at ER-lipid droplet contact sites to organize the machinery needed for lipid droplet biogenesis and adipocyte differentiation, with mutant forms causing cellular dysfunction via disrupted lipid metabolism and toxic accumulation of misfolded protein. No approved therapies target seipin directly; its clinical relevance lies primarily in genetics-driven diagnosis and research on treating its associated syndromes.

Other names

SeipinBSCL2Berardinelli-Seip congenital lipodystrophy type 2 proteinBernardinelli-Seip congenital lipodystrophy type 2 proteinGNG3LGHMN5HMN5CHMND13PELDSPG17seipin lipid droplet biogenesis associatedBerardinelli-Seip congenital lipodystrophy 2 (seipin)

Not targeted therapeutically by small molecules; pathomechanisms in disease primarily arise from loss- or gain-of-function mutations rather than pharmacologic modulation.