GOLPH3L (golgi phosphoprotein 3 like) is a phosphatidylinositol-4-phosphate (PI4P) binding protein that localizes to the Golgi apparatus and plays crucial roles in Golgi organization and protein trafficking 1. Unlike its paralogue GOLPH3, GOLPH3L functions as an antagonist to GOLPH3/MYO18A signaling, producing opposite effects on Golgi morphology despite similar PI4P binding capabilities 1. GOLPH3L exhibits tissue-specific expression patterns, being particularly abundant in secretory tissues, contrasting with the ubiquitous expression of GOLPH3 1. Together with GOLPH3, GOLPH3L serves as a broad-spectrum COPI adaptor that maintains Golgi enzyme localization and ensures proper glycosylation pathway function 2. The protein is essential for maintaining the cis-Golgi localization of the LYSET-GNPT complex, which is critical for mannose 6-phosphate tagging machinery and lysosomal homeostasis 3. GOLPH3L has significant clinical relevance, as it is overexpressed in various cancers including rhabdomyosarcoma and breast cancer, where it promotes tumor cell proliferation and metabolic reprogramming 45. In glioblastoma, GOLPH3L contributes to radiotherapy resistance by suppressing STING-mediated immune responses, making it a potential therapeutic target 6.