ST6GALNAC5 encodes an alpha-2,6-sialyltransferase that catalyzes the addition of sialic acid to gangliosides and glycoproteins, playing critical roles in brain metastasis and cancer progression. The enzyme primarily transfers sialyl groups from CMP-NeuAc to GalNAc residues, contributing to ganglioside biosynthesis 1. Functionally, ST6GALNAC5 expression enhances cancer cell adhesion to brain endothelial cells and facilitates blood-brain barrier penetration, making it a key mediator of breast cancer brain metastasis 2. The protein promotes EGFR sialylation and activation, subsequently activating the PI3K/Akt pathway to drive tumor progression 3. In prostate cancer, ST6GALNAC5 is transcriptionally upregulated by GATA2 and promotes cell invasion, with overexpression correlating with poor prognosis and perineural invasion 4. The enzyme shows decreased interactions with blood-brain barriers when expressed in breast cancer cells, paradoxically suggesting complex regulatory mechanisms 5. Clinically, ST6GALNAC5 serves as both a prognostic biomarker and potential therapeutic target, with its expression being modulated by various regulatory pathways including miR-182 and circular RNAs in different cancer contexts 63.