P4ha1, encoding prolyl 4-hydroxylase 1, is the catalytic subunit of collagen prolyl 4-hydroxylase. It is involved in collagen hydroxylation, consuming α-ketoglutarate (α-KG) in the process. P4ha1 is associated with multiple biological pathways such as glycolysis, TCA cycle, and is important in processes like angiogenesis, cell differentiation, and tumorigenesis [2,6].

Targeting P4ha1 in CD8+ T cells enhances TCF1+ CD8+ T progenitor expansion, mitigates T-cell exhaustion, and enables systemic anti-cancer immunity, indicating its role in tumor-immune escape [2]. In glioblastoma, HIF1α positively and ATF3 negatively regulate P4ha1 transcription, influencing succinate production and PGK1 succinylation, which in turn affects aerobic glycolysis and tumor growth [1]. Down-regulation of P4ha1 in glioma promotes M1 microglia polarization, inhibiting glioma invasiveness [7]. In nasopharyngeal carcinoma, P4ha1 activates HMGCS1 to promote ferroptosis resistance and tumor progression [3]. In esophageal cancer, P4ha1 is overexpressed and promotes cancer progression, and is an independent prognostic factor [4,5].

In conclusion, P4ha1 plays crucial roles in multiple biological processes and diseases. Studies targeting P4ha1 in various models, especially in cancer-related areas, have revealed its importance in tumor-immune regulation, glycolysis, ferroptosis, and tumor progression. Understanding P4ha1 provides potential therapeutic targets for treating related diseases.