Creaming is an issue in UHT milk due to extended storage periods and higher storage temperaturesTherefore, this study aims to unravel the key interfacial mols. and core structure behind the stability of UHT milk fat globules.Raw milk from Holstein, Jersey, and goat breeds, which differ in interfacial components, was selected.The fat globules were standardized for particle size using the UHT system, and stability anal. was performed using Turbiscan to establish high, medium, and low stability fat globule models.Omics anal. revealed that the abundance of 3 interfacial proteins (butyrophilin, adipophilin, and xanthine oxidoreductase) and 2 interfacial phospholipids (phosphatidylserine and sphingomyelin) significantly increased as the fat globule stability increased.Support vector machine was used to identify key interfacial mols.The results showed that the high abundance of butyrophilin, adipophilin, phosphatidylserine, and sphingomyelin contributed to fat globule stability.Mol. docking and CHARMM-GUI further determined that butyrophilin interacted with adipophilin mainly through hydrogen bonds (ΔG = -47.8 kcal/mol and interaction area = 3088.4 Å2).The abundance of this complex in high-stability fat globules was 2.2 times greater than that in medium-stability fat globules and 4.9 times greater than that in low-stability fat globules, resp.We hypothesize that the butyrophilin-adipophilin complex may anchor both the inner monolayer and the outer bilayer, forming the backbone of the entire interface.Therefore, this study first reveals that the key mols. contributing to the stability of UHT milk fat globules are butyrophilin, adipophilin, phosphatidylserine, and sphingomyelin, with the butyrophilin-adipophilin complex serving as the core structure.