P4ha1, encoding prolyl 4-hydroxylase 1, is a key protein kinase. The synthesis and secretion of collagen are related to its sustained activation [4]. It is involved in various pathways such as those related to glycolysis, tricarboxylic acid (TCA) cycle metabolism, and succinate biosynthesis, and is of great biological importance in processes like angiogenesis, cell differentiation, and in the context of multiple diseases [1,2,9]. Genetic models like KO/CKO mouse models can be valuable for studying its functions.

Targeting P4ha1 in CD8+ T cells enhances TCF1+ CD8+ T progenitor expansion and mitigates exhaustion, enabling systemic anti-cancer immunity, indicating its role in cancer immune-escape [2]. In glioblastoma, HIF1α and ATF3 regulate P4ha1 transcription, which affects succinate production and PGK1 succinylation, influencing aerobic glycolysis and tumor growth [1]. In non-alcoholic fatty liver disease, P4ha1 was identified as a hub gene through bioinformatics and machine learning, with its expression down-regulated in a steatosis hepatocyte model [3]. In nasopharyngeal carcinoma, down-regulation of the P4HA1/HMGCS1 axis inhibits tumor growth and metastasis, and high P4ha1 expression predicts poor prognosis [5]. In esophageal squamous cell carcinoma, P4ha1 expression is associated with clinicopathological parameters and is an independent prognostic factor [6]. In esophageal cancer, knockdown of P4ha1 suppresses cell proliferation, collagen synthesis, and promotes apoptosis [7]. In pancreatic ductal adenocarcinoma, knockdown of P4ha1 inhibits glycolytic activity, cell proliferation, chemoresistance, and stemness [8]. In glioma, knockdown of P4ha1 promotes M1 microglia polarization, inhibiting glioma invasiveness [10].

In conclusion, P4ha1 plays essential roles in multiple biological processes and diseases. Model-based research, especially through KO/CKO mouse models, has revealed its significance in cancer, non-alcoholic fatty liver disease, and angiogenesis-related conditions, providing potential therapeutic targets for these diseases.