Mammalian cell membrane phospholipids (PLs) (PLs)

Mammalian cell membrane phospholipids are the fundamental building blocks of the cellular lipid bilayer, primarily consisting of glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine [1, 5]. These molecules provide the structural framework for cells and organelles while actively participating in critical biological functions like signal transduction, vesicle trafficking, and the recruitment of signaling proteins to the membrane surface [1, 2]. In healthy cells, phospholipids are asymmetrically distributed between the inner and outer leaflets of the plasma membrane; however, this asymmetry is often disrupted in diseases such as cancer and viral infections [2, 4]. For instance, the externalization of phosphatidylserine acts as an "eat-me" signal for phagocytes and contributes to an immunosuppressive tumor microenvironment, making it a significant target for therapeutic antibodies like bavituximab [4]. Drugs targeting membrane phospholipids or their metabolic pathways aim to modulate these signaling events or directly disrupt the membrane integrity of pathological cells [3, 4]. However, because phospholipids are ubiquitous in all mammalian cells, achieving high therapeutic indices and avoiding off-target toxicity, such as hemolysis, remains a major hurdle in the development of lipid-targeted therapies [1, 3].

Other names

Membrane phospholipidsGlycerophospholipidsCellular lipidsPhosphoglyceridesMembrane lipid bilayer

Drugs targeting mammalian cell membrane phospholipids function by binding to specific lipid headgroups to modulate immune responses, disrupting the lipid bilayer to induce cell death, or inhibiting enzymes in the phospholipid biosynthetic pathway to alter membrane composition [1, 3, 4].