GOLPH3L, a paralog of GOLPH3, is a phosphatidylinositol-4 -phosphate-binding membrane protein. It plays crucial roles in maintaining Golgi architecture, anterograde trafficking, and is involved in glycosylation pathways. It ensures the cis -Golgi localization of the LYSET -GNPT complex, maintaining the integrity of the M6P -tagging machinery and lysosomal homeostasis [3,5]. GOLPH3L also seems to have an impact on the tumor immune microenvironment and is involved in multiple cancer -related processes [1,2,4,6,8].

Genetic ablation of GOLPH3L in radiotherapy -resistant glioblastoma cells enhanced antitumor immunity and overcame tumor resistance to radiotherapy. This was due to GOLPH3L's interaction with STING after radiotherapy, which led to STING's retrograde transport from Golgi to endoplasmic reticulum, suppressing STING -NLRP3 -mediated pyroptosis and creating an immunosuppressive tumor immune microenvironment [1]. In epithelial ovarian cancer, knockdown of GOLPH3L in cell lines reduced cell viability, and high expression of GOLPH3L was associated with poor prognosis [2]. Similar findings were seen in cervical cancer, where GOLPH3L overexpression was related to advanced staging, metastasis, and poor survival, and its knockdown induced cell cycle arrest, increased apoptosis, and cisplatin sensitivity [6]. In rhabdomyosarcoma, knockdown of GOLPH3L prevented cell proliferation [7]. In ovarian carcinoma, overexpression of GOLPH3L was associated with cisplatin resistance, and its inhibition sensitized cells to cisplatin [8].

In conclusion, GOLPH3L is essential for normal Golgi function and glycosylation. In disease, especially in cancers such as glioblastoma, ovarian, cervical, and rhabdomyosarcoma, GOLPH3L plays significant roles. The use of gene knockout or knockdown models in these studies has revealed its function in tumor growth, metastasis, and response to treatment, suggesting that targeting GOLPH3L could be a potential therapeutic strategy for these cancers.