Hpgd, which encodes 15-Hydroxyprostaglandin dehydrogenase, is crucial for catalyzing the decomposition of prostaglandin E2. This process is involved in multiple biological pathways, and the gene is of significant biological importance in various physiological and pathological conditions [4].

In cholangiocarcinoma, bile exosomal miR-182/183-5p targets Hpgd, increasing prostaglandin E2 generation, which in turn promotes cancer stemness, proliferation, invasion, and epithelial-mesenchymal transition [1].

In hypoxic pulmonary hypertension, down-regulation of Hpgd in human pulmonary artery endothelial cells promotes the disease's development by enhancing cell proliferation, reducing apoptosis, and increasing adhesion and angiogenesis [2].

In liver carcinogenesis, ENO1 promotes cancer progression through YAP1-dependent arachidonic acid metabolism, with HPGD being inversely regulated in this process [3].

In multiple sclerosis, HPGD is downregulated in the spinal cord of EAE mice, and its overexpression alleviates the disease progression by inhibiting M1 microglial polarization, promoting M2 polarization, and activating the PPARγ signaling pathway [4].

Mutations in Hpgd are associated with primary hypertrophic osteoarthropathy, with patients showing features like digital clubbing, periostosis, and acro-osteolysis [5,7,8].

In endometriosis, follicular fluid progesterone downregulates Hpgd in granulosa cells via suppressing the NF-κB signaling pathway, which may be related to ovulatory dysfunction [6].

In summary, Hpgd plays essential roles in multiple biological processes and disease conditions, such as cancer development, pulmonary hypertension, multiple sclerosis, and endometriosis-related ovulatory dysfunction. Its functions are mainly exerted through regulating prostaglandin E2 levels and related signaling pathways. The study of Hpgd using various models helps to understand the underlying mechanisms of these diseases, providing potential targets for treatment.