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Ultra-high pressure homogenization (UHPH) is a promising method for destabilizing and potentially improving the techno-functionality of the egg yolk granule. This study’s objectives were to determine the impact of pressure level (50, 175 and 300 MPa) and number of passes (1 and 4) on the physico-chemical and structural properties of egg yolk granule and its subsequent fractions. UHPH induced restructuration of the granule through the formation of a large protein network, without impacting the proximate composition and protein profile in a single pass of up to 300 MPa. In addition, UHPH reduced the particle size distribution up to 175 MPa, to eventually form larger particles through enhanced protein–protein interactions at 300 MPa. Phosvitin, apovitellenin and apolipoprotein-B were specifically involved in these interactions. Overall, egg yolk granule remains highly stable during UHPH treatment. However, more investigations are needed to characterize the resulting protein network and to evaluate the techno-functional properties of UHPH-treated granule.