PTPRE (protein tyrosine phosphatase receptor type E) is a receptor-type protein tyrosine phosphatase that functions as a negative regulator of immune signaling. In immune cells, PTPRE acts downstream of the high-affinity IgE receptor (FceRI) to suppress cytokine production and degranulation by dephosphorylating key signaling intermediates 1. PTPRE expression is dynamically regulated during macrophage activation; its suppression via the lncRNA PTPRE-AS1 promotes M2 macrophage polarization through MAPK/ERK1/2 pathway modulation 1. Notably, live attenuated yellow fever vaccine transiently reduces PTPRE levels and TCR-mediated T cell activation, contributing to off-target immune suppression 2. Conversely, PTPRE exhibits oncogenic properties in multiple cancers. In thyroid carcinoma, hepatocellular carcinoma, and retinoblastoma, elevated PTPRE promotes cell proliferation, migration, and invasion primarily through AKT and ERK1/2 pathway activation 2, 3, 4. In retinoblastoma, PTPRE knockdown re-sensitizes chemoresistant cells to etoposide through altered SGK3 and AKT phosphorylation 4. CircETV6-mediated upregulation of PTPRE via miR-383-5p targeting drives hepatocellular carcinoma progression 5. Genome-wide studies identify PTPRE rare variants associated with neuroticism and neuropsychiatric traits 6. PTPRE inhibitors show therapeutic promise for cancer treatment 3.