ATP6AP2 (also known as PRR) is required for osteocyte maturation and cortical bone development. To identify downstream effectors of ATP6AP2, plasma membrane-enriched proteins were isolated from control and Atp6ap2-deficient osteoblast-lineage cells and analyzed by mass spectrometry. Comparative proteomic analysis identified MMP14 as a major ATP6AP2-regulated membrane protein. These data support a role for ATP6AP2 in regulating MMP14 surface localization and osteocyte development.