Seipin (BSCL2 lipid droplet morphology-associated protein) (BSCL2)

Seipin, also known as BSCL2 lipid droplet morphology-associated protein, is an integral endoplasmic reticulum (ER) membrane protein essential for the biogenesis and maintenance of lipid droplets (UniProt Q96G97). It functions as a structural scaffold at ER-lipid droplet contact sites, regulating the flow of neutral lipids and ensuring the formation of appropriately sized droplets (Cartwright & Joubert, 2020). Loss-of-function mutations in the BSCL2 gene are the primary cause of Berardinelli-Seip congenital lipodystrophy type 2, a condition marked by a profound lack of adipose tissue, severe insulin resistance, and hepatic steatosis (Magré et al., 2001). Conversely, specific gain-of-toxic-function mutations lead to seipinopathies, a group of motor neuron diseases including Silver syndrome and distal hereditary motor neuropathy (Windpassinger et al., 2004). While Seipin is not currently a direct target for approved small-molecule drugs, it is a significant target for research into metabolic and neurological therapies. Current clinical management for Seipin deficiency involves hormone replacement therapy with metreleptin to address metabolic complications, while experimental approaches explore chemical chaperones like 4-phenylbutyric acid to mitigate the effects of misfolded Seipin variants in neurodegenerative contexts (Szymanski et al., 2007).

Other names

SeipinBSCL2GNG3LGHMN5PPHLBerardinelli-Seip congenital lipodystrophy 2 protein

Regulation of lipid droplet nucleation and growth at endoplasmic reticulum contact sites; chemical chaperone-mediated protein stabilization