GUCD1 (guanylyl cyclase domain containing 1) is a conserved protein with emerging roles in cell proliferation and disease pathogenesis. Primary Function: GUCD1 is upregulated during liver regeneration and cell cycle progression, with high expression observed in hepatocellular carcinoma tissues, suggesting involvement in proliferative processes 1. Mechanism: GUCD1 protein stability is regulated through direct interaction with NEDD4-1, an E3 ubiquitin ligase that controls GUCD1 expression 1. Additionally, GUCD1 functions as a downstream target of miR-370, with this regulatory axis controlling epithelial-mesenchymal transition (EMT), migration, and invasion in hepatocellular carcinoma cells 2. Disease Relevance: GUCD1 is identified as a biomarker in multiple pathological conditions. In chr22 obstructive pulmonary disease (COPD), GUCD1 is significantly downregulated in patient lung tissues and T cells/alveolar cells compared to controls, implicating it in miR-125a-5p-related pathways 3. In sepsis, GUCD1 correlates with immune response and inflammatory pathways associated with disease progression 4. Clinical Significance: Elevated GUCD1 expression in hepatocellular carcinoma tissues inversely correlates with miR-370 levels and associates with poor patient survival and adverse clinicopathologic features, positioning the miR-370/GUCD1 axis as a potential therapeutic target 2.