Reshaping cell fate: Recent advances in CHAC1-mediated pathways of programmed cell death in disease and prognosis

Cation transport regulator homolog-1 (CHAC1), a crucial component of the glutathione (GSH) metabolic pathway, plays a central role in intracellular redox homeostasis. Programmed cell death (PCD) is an active cellular death process initiated by gene regulation in response to internal and external stressors. Previous research has demonstrated that CHAC1 participates in various cell death processes by modulating glutathione metabolism, endoplasmic reticulum stress, and oxidative stress. In this comprehensive review, we first provide an overview of the involvement of CHAC1 in diverse cell death processes, including the apoptosis, ferroptosis, and paraptosis pathways. Emphasizing its molecular complexity, we explore the potential of CHAC1 as a therapeutic target across different PCD modes. Subsequently, this review summarizes the current status of the usage of various drugs targeting CHAC1 and explores the significance of CHAC1 regulation in diverse diseases, including cancer, acute injury, and metabolic disorders, with particular emphasis on its prognostic value and biomarker candidates for cancer. Next, we have critically evaluated CHAC1-centered therapeutic approaches that primarily focused on tumor interventions, while discussing their implications for drug resistance and tumor suppression. Overall, interference with CHAC1 can induce programmed cell death across a spectrum of diseases, thereby providing novel opportunities for targeted therapy.