Galactosidase beta 1 (GLB1) (GLB1)

Galactosidase beta 1 (GLB1), widely known as senescence-associated beta-galactosidase (SA-beta-gal) when detected at pH 6.0, is a lysosomal hydrolase that serves as a primary hallmark of cellular senescence (UniProt P16278). In senescent liver cells, the lysosomal compartment undergoes significant expansion and functional alteration, leading to a marked accumulation of this enzyme (PubMed 32193531). This increased enzymatic activity is exploited in drug development through the design of galactose-modified prodrugs, such as SSK1 and Nav-Gal, which are selectively cleaved within the lysosomes of senescent cells to release potent cytotoxic or senolytic payloads (PubMed 32820865). Targeting this compartment is a key strategy for treating age-related liver diseases, including fibrosis and non-alcoholic steatohepatitis (NASH), by selectively eliminating the senescent cell population that drives chronic inflammation and tissue dysfunction (PMC7443560). However, the presence of GLB1 in non-senescent cells like macrophages necessitates careful drug design to ensure specificity and minimize off-target toxicity.

Other names

Senescence-associated beta-galactosidaseSA-beta-galBeta-galactosidase 1Lysosomal beta-galactosidaseLysosomal compartment of senescent liver cells

Selective prodrug activation by lysosomal beta-galactosidase cleavage; inhibition of lysosomal acidification; induction of lysosomal membrane permeabilization.