Bis(monoacylglycero)phosphate-dependent lysosomal enzyme complex (BMP-enzyme complex)

Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a unique phospholipid found exclusively in the internal membranes of late endosomes and lysosomes [1]. It serves as an essential cofactor and docking platform for several lysosomal hydrolases, most notably acid sphingomyelinase (ASM), acid ceramidase, and various saposin activator proteins [2]. The interaction between BMP and these enzymes is critical for the efficient degradation of sphingolipids and other membrane components. In many lysosomal storage diseases (LSDs), such as Niemann-Pick disease type C and Gaucher disease, the functional integrity of this complex is compromised, leading to the toxic accumulation of lipids [3]. Drugs like arimoclomol target this system by inducing heat shock protein 70 (HSP70), which binds to BMP and stabilizes its interaction with lysosomal enzymes, thereby restoring degradative capacity [4]. This complex represents a vital therapeutic node for addressing lipid metabolism disorders and associated neurodegeneration [5]. [1] Kolter T, Sandhoff K. FEBS Lett. 2010. [2] Kirkegaard T, et al. Nature. 2010. [3] Schulze H, Sandhoff K. Cold Spring Harb Perspect Biol. 2011. [4] FDA. Miplyffa (arimoclomol) Approval. 2024. [5] Hullin-Matsuda F, et al. Prog Lipid Res. 2014.

Other names

LBPA-dependent enzymesLysobisphosphatidic acid-dependent lysosomal hydrolasesBMP-ASM complexBMP-acid sphingomyelinase complexBMP-cofactor complex

Stabilization of the enzyme-cofactor complex via heat shock protein induction or direct enzyme replacement to restore lipid degradation pathways.