Lgals3, also known as Galectin-3, is a β-galactoside-binding protein that belongs to the galectin family. It binds proteins in carbohydrate-dependent and-independent ways and is involved in multiple biological activities such as cell growth, apoptosis, differentiation, angiogenesis, inflammation, fibrosis, and host defense [4]. It is mainly located in the cytoplasm but can shuttle into the nucleus and be secreted.

In the context of kidney stones, knockout of Lgals3 in in vivo models markedly reduces calcium oxalate (CaOx) crystal deposition and renal fibrosis. Lgals3 deficiency also decreases the glycolytic rate and lactate production during CaOx deposition, inhibits histone lactylation of H3K18la, and inhibits the transcription, activation, and expression of FGFR4, suggesting its key role in CaOx stone formation and kidney injury [1]. In glaucoma mouse models, genetic and pharmacologic targeting of Galectin-3 (Lgals3) ameliorated retinal ganglion cell (RGC) degeneration [2]. In diabetes, inhibition of Gal3 (Lgals3) through genetic or pharmacologic loss-of-function improves glucose-stimulated insulin secretion (GSIS) and glucose homeostasis in high-fat diet (HFD)-fed and db/db mice [3].

In conclusion, Lgals3 plays essential roles in various biological processes and disease conditions. Gene knockout mouse models have revealed its significance in kidney stone formation, kidney injury, glaucoma, and diabetes-related β-cell function. Understanding Lgals3 through these models provides insights into disease mechanisms and potential therapeutic targets.