Grhpr, short for Glyoxylate reductase/hydroxypyruvate reductase, is a key enzyme in the glyoxylate cycle. Its deficiency causes primary hyperoxaluria type 2. Although not directly mentioned in the references about gene knockout models, its role in disease is significant [2,4,5].

In hepatocellular carcinoma (HCC), GRHPR expression is downregulated, while miR-138-5p is upregulated. Overexpression of GRHPR suppresses HCC cell proliferation, migration, and invasion, and miR-138-5p promotes HCC cell proliferation and invasive properties by inhibiting GRHPR, regulating PI3K and AKT phosphorylation levels [1]. In addition, GRHPR may be an independent prognostic factor for HCC patients after curative resection, as patients with negative GRHPR in both tumor and non-tumor tissues have a shorter survival time [6].

In primary hyperoxaluria type 2, ethnic differences in GRHPR mutations exist, and different mutations are more prevalent in specific ethnic groups [4]. Also, in monogenic urinary stone disease, missed CNVs in the PH gene GRHPR can be detected by targeted next-generation sequencing [3]. And in metabolic dysfunction-associated steatotic liver disease, GRHPR is identified as a potential therapeutic target [7].

In conclusion, Grhpr plays a crucial role in the glyoxylate cycle and is associated with multiple diseases, including hepatocellular carcinoma, primary hyperoxaluria type 2, monogenic urinary stone disease, and metabolic dysfunction-associated steatotic liver disease. The study of Grhpr helps to understand the mechanisms of these diseases and may provide new strategies for treatment.