PILRB (paired immunoglobulin-like type 2 receptor beta) is an activating immune receptor that associates with ITAM-bearing adapter molecules to regulate cellular signaling and immune function. In gastric cancer, PILRB potentiates oncogenic PI3K/AKT signaling by binding and stabilizing IRS4 protein, protecting it from ubiquitin-mediated degradation 1. PILRB also reprograms cholesterol metabolism and confers resistance to statin therapy in gastric cancer cells 1. In neurodegenerative diseases, PILRB emerges as a disease-associated protein. Mendelian randomization studies identified genetically predicted PILRB abundance as causally associated with Alzheimer's disease risk 2 and with reduced caudate nucleus volume 3. PILRB was identified among seven proteins with structural alterations due to missense mutations in Alzheimer's disease 4. In microglia-like cells derived from monocytes, disease risk haplotypes at the PILRB locus drive altered gene expression, a cell-type-specific effect not observed in peripheral blood monocytes 5. Additionally, PILRB variants regulate its abundance through 3'UTR-mediated mechanisms relevant to age-related macular degeneration 6. Clinically, PILRB expression levels correlate with prognosis in glioblastoma and prostate cancer, positioning it as a potential prognostic biomarker 78. These findings establish PILRB as both an oncogenic driver and a causal protein biomarker for neurodegenerative disease pathogenesis.