Adh5, also known as alcohol dehydrogenase 5 (class III), chi polypeptide, is a key enzyme involved in multiple biological processes. It metabolizes S-nitrosoglutathione (GSNO) to regulate cellular S-nitrosothiol (SNO) levels, playing a crucial role in maintaining redox and nitroso-redox homeostasis. This function is associated with pathways like the stimulator of interferon genes (STING)-dependent innate immune response and the regulation of brown adipose tissue (BAT) thermogenesis [1,2].

In genetic models, Adh5 deficiency in mice leads to defective STING-dependent immune responses upon microbial challenge, facilitating viral replication, which reveals its importance in host defense against pathogens [1]. In BAT, loss of Adh5 impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction, indicating its role in regulating adipose thermogenesis and metabolic homeostasis [2].

In conclusion, Adh5 is essential for maintaining SNO homeostasis, which is crucial for STING-mediated innate immune responses against pathogens and for regulating adipose thermogenesis and metabolic homeostasis. Studies using Adh5 knockout mouse models have provided valuable insights into its role in these disease-relevant biological processes.