Calcium homeostasis plays a major role in cellular physiology, and its dysregulation can lead to cell death. The Plasma Membrane Calcium ATPase (PMCA) plays a key role in calcium efflux from the cytosol towards the extracellular space to terminate calcium signaling. Biotin absorption is also crucial for cellular physiology and development, and its deficiency leads to severe conditions. The sodium-dependent multivitamin transporter (SMVT) plays an essential role in biotin uptake. Therefore, their intracellular localization is critical for their function in calcium homeostasis and biotin absorption, respectively. However, the molecular mechanisms involved in the regulation of the distribution of PMCA isoforms and SMVT to specific membrane domains remain partially resolved. Genetic studies and functional analysis highlight the involvement of PLEKHA7, a cytoplasmic junctional protein, in regulating calcium homeostasis. PLEKHA7 recruits to apical junctions the small adaptor protein PDZD11 to control the localization of plasma membrane-associated proteins. Similarly to PLEKHA7, PLEKHA5 and PLEKHA6 interact with PDZD11 and recruit the protein to distinct plasma membrane localizations. PDZD11 interacts with the C-terminus of PMCA b-isoforms and SMVT.