Phospholipase B1 (PLB1)

Phospholipase B1 (PLB1) is a calcium-independent, membrane-associated enzyme that catalyzes the complete hydrolysis of phospholipids by cleaving fatty acyl chains at both the sn-1 and sn-2 positions on the glycerol backbone, combining phospholipase A2 and lysophospholipase activities[1][2][3]. It demonstrates broad substrate specificity, preferentially hydrolyzing at the sn-2 position in diacylglycerols and diacylphospholipids, and also acts as a retinyl ester hydrolase and lipase[1][2][3]. In humans, PLB1 is involved in the digestion and absorption of dietary lipids and retinoids at the intestinal brush border[1][2]. In pathogenic fungi such as *Cryptococcus neoformans* and *Candida albicans*, PLB1 is a critical virulence factor, promoting brain colonization, immune evasion, tissue invasion, and CNS pathology; genetic inactivation of PLB1 attenuates virulence and increases susceptibility to host immune defenses[6][4]. PLB1 has been associated with several diseases, notably fungal infections (particularly fungal meningoencephalitis in immunocompromised individuals), prostate cancer, and has been identified as a genetic risk factor for rheumatoid arthritis[1][6]. Currently, PLB1 is considered a promising but as yet unexploited therapeutic target, especially in the treatment of invasive fungal infections, but no drugs directly targeting human or fungal PLB1 are clinically available[1][6].

Other names

Membrane-associated phospholipase B1LysophospholipasePhospholipase BPhospholipase A2 (non-canonical but sometimes used due to overlapping activity)PLB/LIPTriacylglycerol lipaseLipaseLecithinase BLysolecithinase

For future drugs: Putative mechanisms include competitive or irreversible enzyme inhibition, reducing fungal virulence and host tissue damage through blockade of lipid remodeling and attenuation of eicosanoid signaling and capsular modification[6]. Pharmacological inhibition may reduce pathogen survival, virulence, and immune evasion in infections[6].