HKDC1, or hexokinase domain component 1, is an important protein with functions in multiple biological processes. It is involved in glucose metabolism, lipid homeostasis, and has been associated with pathways related to cell proliferation, metastasis, and immune evasion. HKDC1 is also known to interact with various proteins and RNAs, playing a role in the regulation of gene expression and metabolism [1-10]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable in further understanding its functions.

In gastric cancer, HKDC1 enhances invasion, migration, and cisplatin resistance by reprogramming lipid metabolism. It forms a ribonucleoprotein complex with G3BP1 to stabilize PRKDC transcript [1]. In hepatocellular carcinoma, HKDC1 promotes tumor immune evasion in a CD8+ T cell-dependent manner by activating STAT1/PD-L1 [2]. In pancreatic adenocarcinoma, HKDC1 promotes autophagy and cell proliferation through interaction with PARP1 and poly(ADP-ribosyl)ation [6]. In liver cancer, HKDC1 promotes stemness under hypoxia by stabilizing β-catenin [3]. In gastric cancer, silencing HKDC1 inhibits cell proliferation and glycolysis [5]. Also, HKDC1 upregulation promotes glycolysis, disease progression, and chemoresistance in gastric cancer [4]. In intrahepatic cholangiocarcinoma, HKDC1 is identified as a potential prognostic biomarker associated with metabolic reprogramming [7]. In the liver, HKDC1 expression contributes to liver metabolism, and its overexpression causes mitochondrial dysfunction in hepatocytes [8].

In conclusion, HKDC1 plays essential roles in various biological processes and disease conditions. Model-based research, especially KO/CKO mouse models, has revealed its significance in cancer metastasis, immune evasion, autophagy, cell proliferation, and metabolic regulation. These findings suggest that HKDC1 could be a potential therapeutic target for cancers and liver-related metabolic diseases.