GCLC

The GCLC gene encodes the glutamate-cysteine ligase catalytic subunit (GCLC), a core component of the rate-limiting enzyme in glutathione (GSH) biosynthesis. Common aliases include GLCL and GCS catalytic subunit. GCLC forms a heterodimer with the modifier subunit GCLM to catalyze glutamate and cysteine condensation into γ-glutamylcysteine, the first step in GSH synthesis. It is regulated by the Nrf2-ARE pathway, which upregulates GCLC under oxidative stress.
Dysregulated GCLC links to diverse diseases: reduced levels drive oxidative damage in neurodegenerative disorders (e.g., Alzheimer’s) and liver diseases like non-alcoholic steatohepatitis; overexpression in cancers boosts GSH-mediated chemo-resistance. Preclinical studies test GCLC inhibitors as chemo-adjuvants to sensitize tumors, though clinical trials remain early-stage.