LGALS3 encodes galectin-3, a β-galactoside-binding lectin that functions as a multifaceted regulator in cellular processes and disease pathogenesis 1. The protein serves diverse biological functions including cell growth, apoptosis, pre-mRNA splicing, differentiation, inflammation, and fibrosis 1. LGALS3 acts as a sensitive sensor of lysosomal membrane damage, rapidly translocating to compromised lysosomes and coordinating autophagy responses through formation of the LGALS3-SMURF1-PPP3/calcineurin complex, which activates TFEB for lysosomal biogenesis 23. In disease contexts, LGALS3 promotes pathological processes through multiple mechanisms. It enhances calcium oxalate crystal formation and kidney injury by interacting with PKM2 and promoting histone lactylation-mediated FGFR4 activation 4. In IgA nephropathy, LGALS3 activates the NLRP3 inflammasome and promotes Th17 cell differentiation, worsening kidney pathology 5. The protein impairs pancreatic β-cell function by binding CACNG1 and inhibiting calcium influx, contributing to diabetes pathogenesis 6. In tauopathy, LGALS3 aggravates microglial activation and enhances tau transmission through extracellular vesicles 7. Additionally, LGALS3 facilitates glioblastoma progression by promoting mesenchymal transition and macrophage polarization 8. These diverse pathological roles make LGALS3 an attractive therapeutic target across multiple diseases 1.