GLOD4, glyoxalase domain containing protein 4, belongs to the glyoxalase gene family, yet its physiological role remains relatively unknown compared to some family members [4]. The common feature of this family is the presence of structural motifs coordinating divalent cations for enzyme activity, with functions related to metabolism and aldehyde detoxication [4].

In Alzheimer's disease (AD) research, GLOD4 mRNA and protein isoforms were downregulated in cortical tissues from AD patients [1]. In Blmh -/- 5xFAD mouse AD models, Glod4 mRNA was downregulated, associated with elevated Aβ and worsened memory/sensorimotor performance [1]. In N2a-APPswe cells, Glod4 depletion upregulated AβPP and downregulated autophagy-related genes, suggesting GLOD4 interacts with AβPP and the autophagy pathway [1].

In the study of testicular development, in Tibetan sheep, GLOD4 expressions at both mRNA and protein levels were significantly higher in 1-year-old and 3-year-old testes compared to 3-month-old ones, and the protein was mainly localized in the cytoplasm of Leydig cells, indicating its possible role in Leydig cell development [2]. In Qianbei Ma goats, GLOD4 was mainly expressed in Leydig cells. Silencing GLOD4 suppressed testosterone secretion-related and cell cycle-related genes, blocked the cell cycle at G2/M phase, and reduced testosterone secretion, while overexpression had the opposite effects, suggesting its influence on cell development via cell cycle, proliferation, and testosterone synthesis [3].

In Caenorhabditis elegans, glod-4 mutation led to increased food intake, and RNAseq analysis identified upregulation of several neurotransmitters and feeding genes [5].

In conclusion, through studies in models like mice and nematodes, GLOD4 has been shown to be involved in processes such as Alzheimer's disease-related Aβ regulation and autophagy, as well as testicular cell development and feeding behavior in nematodes. These model-based studies have provided valuable insights into the role of GLOD4 in specific biological processes and disease-related conditions [1,2,3,5].