PROZ, also known as the gene encoding vitamin K-dependent protein Z, is a gene with significant biological importance. Protein Z is a vitamin K-dependent plasma protein that is canonically considered to have anticoagulant effects through negative regulation of factor Xa [3,4]. It may also be involved in other biological processes as it has been associated with various diseases, indicating its role in different physiological pathways. Genetic models can be valuable for further exploring its functions.

In hepatocellular carcinoma, low PROZ expression is significantly correlated with poor prognosis. PROZ is closely related to the expression of p-ERK and VEGFR2, and its down-regulation in sorafenib-resistant strains is accompanied by increased p-ERK and decreased VEGFR2. Also, PROZ is negatively correlated with genes related to immunotherapy efficacy and T-cell infiltration in tumor tissue, suggesting it may serve as a potential target to improve the efficacy of targeted combined immunotherapy [1]. In early hepatocellular carcinoma, PROZ expression is decreased compared to normal liver controls, and low PROZ expression might result in poor overall survival [2].

Loss-of-function in PROZ is associated with an increased risk of non-cardioembolic ischemic stroke in the UK Biobank, consistent with its role as an anticoagulant factor [3]. In a multi-ethnic study of young and middle-aged adults, there was evidence of a non-linear positive association between PZ level (encoded by PROZ) and unexplained stroke, with genetic variants related to PZ levels also showing an association with cryptogenic stroke [4].

PROZ levels are decreased in patients with prediabetes and type 2 diabetes, and there are negative correlations between PROZ and fasting plasma glucose and hemoglobin A1c, suggesting it may be a biomarker for early detection of prediabetes [5].

In preterm birth, increased PROZ expression in amniotic fluid is associated with the occurrence of PTB, and PROZ promotes the proliferation and migration of amniotic membrane fibroblasts [6]. Polymorphisms of PROZ gene are associated with recurrent spontaneous abortion in Chinese Han women [7].

In conclusion, PROZ, encoding protein Z, has a crucial role in multiple biological processes, especially in coagulation. Its dysregulation is associated with various diseases such as hepatocellular carcinoma, ischemic stroke, diabetes, preterm birth, and recurrent spontaneous abortion. Studies, especially those related to loss-of-function, have provided insights into its role in these disease conditions, which may help in developing new diagnostic and therapeutic strategies.