Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR)

The **Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR)** is a 428-amino acid extracellular and membrane-associated protein that combines immunoglobulin-like (IgSF) domains with multiple leucine-rich repeat (LRR) motifs. The protein is highly expressed in mesenchymal stromal/stem cells, brown adipose tissue, skeletal muscle, and multiple other tissues including retina, heart, ovary, and testis. ISLR functions in cell adhesion, signaling within the extracellular matrix, and regulation of mitochondrial activity and energy homeostasis. Mechanistically, ISLR interacts with Ndufs2 to modulate IL-6 signaling, acting as a brake to prevent excess brown fat activation following muscle injury, thereby affecting whole-body energy expenditure and thermogenesis. Because of its regulatory role in muscle-adipose tissue communication and metabolic function, ISLR represents a promising novel target for metabolic disease therapeutics, although direct pharmacological targeting has not yet reached clinical application. Additionally, ISLR may serve as a marker for specific stem cell populations and is involved in developmental processes.

Other names

ISLRMeflinHsT17563mesenchymal stromal-cell and fibroblast-expressing Linx paralogueimmunoglobulin superfamily containing leucine-rich repeat

Modulates IL-6 signaling by interacting with NADH:Ubiquinone oxidoreductase core subunit S2 (Ndufs2)\nActs as a brake on muscle-derived IL-6, limiting brown adipose tissue activation and thermogenesis