LRPAP1 (LDL receptor related protein associated protein 1) functions as a molecular chaperone and antagonist for LDL receptor-related proteins, regulating their activity along the secretory pathway 1. The protein is normally retained in the endoplasmic reticulum but can be secreted under specific conditions. Activated microglia release nanomolar levels of LRPAP1 during inflammatory activation or ER stress, where it inhibits microglial phagocytosis of synapses and amyloid-beta (Aβ) uptake, and prevents Aβ aggregation 2. LRPAP1 has significant pathological relevance as secreted LRPAP1 binds to the extracellular domain of IFNAR1, triggering its ubiquitination and degradation, thereby facilitating viral evasion from cellular innate immunity in infections by SARS-CoV-2 and EV71 3. Disease associations include neurodegenerative disorders, where the LRPAP1 D allele significantly increases susceptibility to degenerative dementias 4 and Parkinson's disease, particularly when combined with APOE ε4 variants 5. Clinically, LRPAP1-derived peptides are being investigated as cancer vaccines, with TEIPP24 showing promise in checkpoint-resistant non-small cell lung cancer by inducing specific T-cell responses 6.