Electrogenic Na⁺/HCO₃⁻ cotransporter 1 (NBCe1), encoded by SLC4A4, regulates intra- and extracellular pH, and its dysfunction is associated with neurological manifestations. Among the major NBCe1 isoforms, NBCe1-C is predominantly expressed in the brain and possesses a unique C-terminal -ETTL sequence that constitutes a class I PDZ-binding motif. However, the functional significance of this motif remains unclear. Using an NBCe1-C-specific antibody, we found that NBCe1-C was predominantly expressed in astrocytes in primary rat hippocampal cultures and enriched at the distal tips of astrocytic processes. We therefore examined the role of the -ETTL motif in NBCe1-C stability, cell-surface expression, and endocytosis using heterologous expression systems. Disruption of the -ETTL motif did not affect protein stability but significantly reduced cell-surface expression. Unexpectedly, the motif also promoted NBCe1-C internalization, suggesting that it facilitates dynamic trafficking between the plasma membrane and intracellular compartments rather than simply stabilizing NBCe1-C at the cell surface. Under amino acid-starved conditions accompanied by LC3-II accumulation, cell-surface expression of wild-type NBCe1-C was markedly reduced, whereas that of the -ETTL mutant was largely unchanged. Furthermore, sorting nexin 27 (SNX27) interacted with NBCe1-C in a manner dependent on both the -ETTL motif and the SNX27 PDZ domain. These findings identify the -ETTL motif as a key determinant of NBCe1-C membrane trafficking and SNX27 as its PDZ-dependent binding partner, potentially contributing to dynamic regulation of NBCe1-C in astrocytic processes.