Isoform 3 of Seipin

Seipin (Isoform 3, encoded by BSCL2) is a lipid droplet-associated protein involved in lipid metabolism and organelle biogenesis (UniProt: Q96G97-4). The protein plays a role in adipocyte differentiation and triglyceride accumulation, with mutations linked to Berardinelli-Seip congenital lipodystrophy. In humans, seipin is widely expressed across tissues and contributes to endoplasmic reticulum and lipid droplet homeostasis.

In Alzheimer's disease, BSCL2 Isoform 3 shows reduced abundance in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.40 across subcellular fractions (Chaparral AD proteomics). This downregulation was detected via TMT-labeled quantitative proteomics across four subcellular compartments (P2, P3, S2, S3), suggesting impaired lipid metabolism in the AD brain. The decreased expression may reflect disrupted lipid homeostasis as part of AD pathophysiology, though functional consequences remain to be established.