GPD1L (glycerol-3-phosphate dehydrogenase 1-like) is a metabolic enzyme with context-dependent roles in disease. In cardiac tissue, GPD1L regulates cardiac sodium current through NAD(H) balance and modulation of SCN5A phosphorylation, with mutations associated with Brugada syndrome type 2, though cardiac-specific functional data from the provided abstracts is limited. In cancer metabolism, GPD1L exhibits dual roles depending on tumor type. In hepatocellular carcinoma (HCC), GPD1L is significantly upregulated and promotes tumor progression by facilitating glycerol-3-phosphate (G3P) and triacylglycerol synthesis 1, with high expression correlating with venous invasion, shorter survival, and reduced therapeutic response 2. GPD1L knockdown suppresses HCC invasiveness and stemness 1. The G3P produced by GPD1L accumulates in the tumor microenvironment and impairs CD8+ T cell function by inhibiting LCK kinase activity in TCR signaling 3. Conversely, in renal cell carcinoma (RCC and ccRCC), GPD1L functions as a tumor suppressor, with downregulation promoting progression through enhanced regulatory T cell infiltration and lipid metabolism reprogramming 45. In RCC, GPD1L promotes PINK1/Parkin-mediated mitophagy 5. Additionally, GPD1L participates in hypoxic glycerol excretion pathways that balance reductive and energetic stress during cellular transformation 6, and may be therapeutically relevant in obesity through adipose tissue regulation 7.