This project investigates the shell matrix proteome of the nacreous layer of the pearl oyster Pinctada fucata. Nacre powders were subjected to an optimized extraction workflow combining EDTA-mediated decalcification and SDS/DTT-based solubilization to obtain three fractions: EDTA-soluble matrix (ESM), SDS-soluble matrix (SSM) and insoluble matrix (ISM). Each fraction was analysed by nanoLC-MS/MS using data-independent acquisition (DIA), and proteins were identified and quantified using a complete genome-derived database with intensity-based absolute quantification (iBAQ). The resulting dataset provides fraction-resolved protein abundances, solubility-based type classifications and functional annotations (including BLAST and conserved domain searches), and serves as a quantitative reference for comparative studies of molluscan shell biomineralization.