TLCD4 (TLC domain containing 4) is a protein with documented roles in lipid homeostasis and endoplasmic reticulum localization [GO annotations]. Recent evidence suggests TLCD4 functions as a metabolic biomarker responsive to cold exposure and lipid mobilization. In animal models (ferrets and rats), one week of cold exposure at 4°C consistently upregulated Tlcd4 expression in adipose tissue depots and peripheral blood mononuclear cells (PBMCs), making it a potential biomarker of metabolic adaptation to cold 1. The gene showed differential expression patterns depending on exposure duration and tissue type, with acute cold exposure reducing Tlcd4 mRNA in some white adipose tissue depots 1. Clinical relevance emerges from associations with disease pathology: TLCD4 was identified as one of three genes with moderate discriminatory performance in distinguishing sepsis-induced acute respiratory distress syndrome (ARDS) from uncomplicated sepsis, suggesting involvement in inflammatory responses 2. Its protein-binding capacity and ER localization indicate roles in cellular protein interactions and lipid trafficking. While human studies showed variable TLCD4 responses to acute cold exposure depending on metabolic status 1, the gene represents a promising molecular marker for monitoring metabolic and inflammatory states, though further investigation is needed to clarify its precise mechanistic function.