Lipolysis-stimulated lipoprotein receptor (LSR) (LSR)

The Lipolysis-stimulated lipoprotein receptor (LSR), also known as LISCH7, is a transmembrane protein that plays a pivotal role in both systemic lipid metabolism and the structural integrity of epithelial barriers (UniProt Q86X29). In the liver, LSR mediates the uptake of triglyceride-rich lipoproteins in a process stimulated by free fatty acids, making it essential for postprandial lipid clearance (Yen et al., 1999, J. Biol. Chem.). Additionally, LSR is a key component of tricellular tight junctions, where it recruits tricellulin to seal the convergence of three cells, thereby maintaining the blood-brain barrier and epithelial impermeability (Masuda et al., 2011, J. Cell Sci.). In the context of oncology, LSR mRNA and protein are frequently overexpressed in cancers such as breast, colon, and ovary, where they promote cell survival and migration (Shimada et al., 2017, Cancer Sci.). Targeting LSR mRNA via RNA interference (siRNA) or antisense oligonucleotides (ASOs) is an emerging strategy to reduce these pro-tumorigenic effects by downregulating protein expression. However, therapeutic intervention must account for potential safety concerns, including disrupted lipid homeostasis and increased permeability of the blood-brain barrier (Stamatovic et al., 2019, Front. Oncol.).

Other names

LISCH7Angio-associated lipolysis-stimulated lipoprotein receptorLipolysis-stimulated receptorLSR mRNA

RNA interference-mediated degradation of LSR mRNA or antisense-mediated inhibition of translation to reduce LSR protein levels (Takahashi et al., 2016). Additionally, the LSR protein itself can be targeted by monoclonal antibodies to neutralize its activity or by bacterial toxins that utilize it as a cellular entry receptor (Gibert et al., 2011).