Tlcd4, whose exact function and associated pathways are yet to be comprehensively defined, is emerging as a gene of interest in multiple biological contexts. It could potentially play roles in processes related to metabolic adaptation, collagen regulation, and sepsis-induced ARDS, suggesting its importance in metabolism, tissue remodeling, and immune-related disease mechanisms [1,2,3].

In the context of cold exposure, in animal models (ferrets and rats), Tlcd4 was affected in adipose tissue (AT) and peripheral blood mononuclear cells (PBMCs). One week of cold exposure (4 °C) led to Tlcd4 overexpression in aortic perivascular and inguinal AT depots and PBMCs in ferrets, and in brown AT and PBMCs in rats. In contrast, short-term cold exposure (1 h at 4 °C) reduced Tlcd4 mRNA levels in retroperitoneal white AT in rats. In humans, decreased PBMC TLCD4 expression was seen in normal-weight women after acute cold exposure, potentially due to short-term fasting during the procedure [1].

In scleral fibroblasts, transcriptome analysis identified Tlcd4 as one of the genes affected by hypoxia and alpha-ketoglutaric acid, which influence collagen expression, offering new insights into myopia prevention and treatment [2].

In sepsis-induced ARDS, feature selection analysis showed that Tlcd4, along with PRSS30P and ZNF493, had moderate performance in differentiating sepsis-induced ARDS from sepsis [3].

In conclusion, Tlcd4 appears to be involved in metabolic responses to cold, collagen regulation in scleral fibroblasts, and the differentiation of sepsis-induced ARDS from sepsis. The studies in animal models, especially in the context of cold exposure, have provided valuable insights into its potential role in metabolic adaptation. Understanding Tlcd4 may offer new perspectives for developing therapies related to cold-mimicking treatments, myopia prevention, and early diagnosis of sepsis-induced ARDS.