CNPY3 (canopy FGF signaling regulator 3) functions as a critical co-chaperone for HSP90B1/GRP94 in the endoplasmic reticulum, specifically required for proper folding and trafficking of Toll-like receptors (TLRs) except TLR3 1. CNPY3 controls TLR exit from the ER and surface expression, consequently regulating both innate and adaptive immune responses 2. Beyond TLR regulation, CNPY3 plays a TLR-independent role in NLRP3-inflammasome activation by regulating caspase-1 localization and autoactivation, affecting IL-1β and IL-18 processing 1. Disease associations include developmental and epileptic encephalopathy 60, where loss-of-function variants impair both TLR signaling and inflammasome activation 1. A novel C52Y variant identified in familial neuromyelitis optica spectrum disorder shows dominant negative effects on TLR4 surface expression and reduces inflammatory cytokine production 2. Additionally, CNPY3 appears to promote cancer progression in multiple malignancies including breast, colon, and prostate cancers by modulating the tumor microenvironment and enhancing cell migration and invasion 34. The protein's dual roles in immune regulation and cancer progression make it a potential therapeutic target with clinical significance in both inflammatory diseases and oncology.