PLPP5 (phospholipid phosphatase 5) is a magnesium-independent phospholipid phosphatase with broad substrate specificity that preferentially catalyzes conversion of diacylglycerol pyrophosphate into phosphatidate, while also acting on phosphatidate and lysophosphatidate 1. The enzyme participates in both lipid synthesis and generation/degradation of lipid-signaling molecules 1. Clinically, PLPP5 has emerged as a notable gene in cancer genomics. It is frequently amplified at the 8p11.23 locus, one of the most common copy-number alterations in squamous lung carcinomas, breast cancers, and squamous esophageal carcinomas, with concomitant mRNA overexpression 23. PLPP5 has been proposed as a putative "driver" gene in 8p11.23-amplified cancers 3. A novel PLPP5-FGFR1 fusion has been identified in lung squamous cell carcinoma, representing a new translocation partner for FGFR1 4. Additionally, PLPP5 shows potential as a plasma-derived extracellular vesicle biomarker for digestive system cancer prediction 5 and has been identified as a B cell marker gene associated with triple-negative breast cancer prognosis and immunotherapy response 6. Notably, loss-of-function mutations in PLPP5 appear dispensable for normal B lymphocyte development and antibody production 7.