Objective To explore the expression and potential clinical value of Discs large homologyassociated protein 5 (DLGAP5) in hypoxic pulmonary hypertension (HPH). Methods The transcriptome data of non-HPH patients and HPH patients were downloaded from the GEO database, and bioinformatics analysis was performed to explore the expression of DLGAP5 in the non-HPH patients and HPH patients. Then, lung tissue samples from 9 HPH cases and 4 non-HPH cases were collected, and the expression levels of DLGAP5 in different lung tissues were verified using Western blot experiments. Rat models of HPH were created using Sugen5416 combined with chronic hypoxia ( SuHx) and the mean pulmonary artery pressure (mPAP) was detected. The rats were divided into HPH rat model group and normal group, with 6 rats in each group. Pulmonary vascular remodeling and DLGAP5 expression in HPH were detected by hematoxylin-eosin ( HE), immunohistochemistry ( IHC), and immunofluorescence (IF) staining. Finally, differential gene enrichment analysis was used to explore the downstream signaling pathway of DLGAP5 in regulating HPH. Results DLGAP5 was significantly upregulated in lung tissues from HPH patients (P<0. 01). Compared with the normal group, the mPAP was significantly increased in SuHxinduced HPH rat model group (P<0. 0001). HE and IHC staining showed a thickened pulmonary artery media and obvious vascular remodeling in HPH rat model group. IF staining showed increased DLGAP5 expression in pulmonary artery media smooth muscle cells in HPH rat model group compared with the normal group (P<0. 0001), mainly distributed in the cytoplasm. Finally, differential gene enrichment analysis suggested that DLGAP5 may regulate HPH by influencing the cell cycle, especially the G2 / M phase (P<0. 001). Conclusions DLGAP5 may be a potential new target for HPH, indicating new ideas for the diagnosis and treatment of HPH.